Conformationally stabilized HIV envelope immunogens and triggering HIV-I envelope to reveal cryptic V3-loop epitopes

ABSTRACT

Stabilized forms of gp120 polypeptide, nucleic acids encoding these stabilized forms, vectors comprising these nucleic acids, and methods of using these polypeptides, nucleic acids, vectors and host cells are disclosed. Crystal structures and computer systems including atomic coordinates for stabilized forms of gp120, and gp120 with an extended V3 loop, and methods of using these structures and computer systems are also disclosed.

CROSS REFERENCE TO RELATED APPLICATION

This is the U.S. §371 National Stage of International Application No. PCT/US2006/034681, filed Sep. 6, 2006, published in English under PCT Article 21(2), which in turn claims the benefit of U.S. Provisional Application No: 60/713,725, filed Sep. 6, 2005; U.S. Provisional Application No: 60/729,878, filed Oct. 24, 2005; U.S. Provisional Application No: 60/731,627, filed Oct. 28, 2005; and U.S. Provisional Application No: 60/832,458, filed Jul. 20, 2006. All of the provisional applications are incorporated by reference herein in their entirety.

FIELD

The present disclosure relates to stabilized forms of human immunodeficiency virus gp120 envelope protein, specifically to crystalline forms of gp120, high resolution structures obtained from these crystals, and use thereof.

BACKGROUND

The primary immunologic abnormality resulting from infection by human immunodeficiency virus (HIV) is the progressive depletion and functional impairment of T lymphocytes expressing the CD4 cell surface glycoprotein. The loss of CD4 helper/inducer T cell function probably underlies the profound defects in cellular and humoral immunity leading to the opportunistic infections and malignancies characteristic of the acquired immunodeficiency syndrome (AIDS) (Lane et al., Ann. Rev. Immunol. 3:477, 1985). Studies of HIV-1infection of fractionated CD4 and CD8 T cells from normal donors and AIDS patients have revealed that depletion of CD4 T cells results from the ability of HIV-1 to selectively infect, replicate in, and ultimately destroy this T lymphocyte subset (Klatzmann et al., Science 225:59, 1984). The possibility that CD4 itself is an essential component of the cellular receptor for HIV-1 was first indicated by the observation that monoclonal antibodies directed against CD4 block HIV-1 infection and syncytia induction (Dalgleishet al., Nature 312:767, 1984; McDougal et al., J. Immunol. 135:3151, 1985). This hypothesis has been confirmed by the demonstration that a molecular complex forms between CD4 and the major envelope glycoprotein of HIV-1 (McDougal et al., Science 231:382, 1986).

The major envelope protein of HIV-1 is a glycoprotein of approximately 160 kD (gp160). During infection proteases of the host cell cleave gp160 into gp120 and gp41. gp41 is an integral membrane protein, while gp120 protrudes from the mature virus. Together gp120 and gp41 make up the HIV envelope spike.

The HIV envelope spike mediates binding to receptors and virus entry (Wyatt and Sodroski, Science 280:188, 1998). The spike is trimeric and composed of three gp120 exterior and three gp41 transmembrane envelope glycoproteins. CD4 binding to gp120 in the spike induces conformational changes that allow binding to a coreceptor, either CCR5 or CXCR4, which is required for viral entry (Dalgleish et al., Nature 312:763, 1984; Sattentau and Moore, J. Exp. Med. 174:407, 1991; Feng at al., Science 272:872, 1996; Wu et al., Nature 384:179, 1996; Trkola et al., Nature 384:184, 1996).

The mature gp120 glycoprotein is approximately 470-490 amino acids long depending on the HIV strain of origin. N-linked glycosylation at approximately 20-25 sites makes up nearly half of the mass of the molecule. Sequence analysis shows that the polypeptide is composed of five conserved regions (C1-C5) and five regions of high variability (V1-V5).

With the number of individuals infected by HIV-1 approaching 1% of the world's population, an effective vaccine is urgently needed. An enveloped virus, HIV-1 hides from humoral recognition behind a protective lipid bilayer. An available viral target for neutralizing antibodies is the envelope spike. Genetic, immunologic and structural studies of the HIV-1 envelope glycoproteins have revealed extraordinary diversity as well as multiple overlapping mechanisms of humoral evasion, including self-masquerading glycan, immunodominant variable loops, and conformational masking. These evolutionarily honed barriers of diversity and evasion have confounded traditional means of vaccine development. It is believed that immunization with effectively immunogenic HIV gp120 envelope glycoprotein can elicit a neutralizing response directed against gp120, and thus HIV. The need exists for immunogens that are capable of eliciting an immunogenic response in a suitable subject. In order to be effective, the antibodies raised must be capable of neutralizing a broad range of HIV strains and subtypes.

SUMMARY OF THE DISCLOSURE

Disclosed herein are gp120 polypeptides and nucleic acid molecules encoding gp120 polypeptides, which are useful to induce an immunogenic response to a lentivirus, such as SIV or HIV (for example HIV-1 and HIV-2) in a subject. In several embodiments, the gp120 polypeptides are stabilized in a CD4 bound conformation by the introduction of a plurality of non-naturally occurring cross-linking cysteine residues. In other examples, the gp120 polypeptide has the V3 loop in an extended conformation.

Immunogenic compositions containing a therapeutically effective amount of gp120 polypeptides and nucleic acid molecules encoding gp120 polypeptides are also disclosed. Also disclosed are methods for eliciting and/or enhancing an immune response in a subject, for example by administering an immunogenic composition.

Crystalline forms of gp120 are disclosed as are crystal structures of gp120 polypeptides obtained from these structures. Methods are also disclosed for identifying an immunogen that induces an immune response to gp120 using these crystal structures. Also provided by this disclosure is a machine readable data storage medium including a data storage material encoded with machine readable data corresponding to the coordinates of the crystal structures disclosed herein. A computer system is disclosed for displaying the coordinate data from these crystal structures of gp120, such as the atomic positions, surface, domain, or region of the gp120 polypeptide.

The foregoing and other objects, features, and advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of the development cycle for gp120 immunogens stabilized in the CD4-bound conformation. Qualitative Biacore analysis was used as an initial screen to determine if CD4 and the CD4 induced (CD4i) antibodies still bound. Isothermal titration calorimetry (ITC) and crystal structure determination were used to refine the gp120 immunogens.

FIG. 2 is a set of computer generated images. The images show the modeled structures of wild-type gp120 compared with cavity-filling and double cysteine mutants. Each pair of panels shows the HXBc2 core wild-type structure (left panels) and the mutant structure (right panels). Data ranged from minimum Bragg spacings of 1.9 A to 2.5 A.

FIG. 3 is a set of computer generated images. The images show the positions of conformationally stabilizing mutations in the CD4-bound structure of HIV-1 (left) and the unliganded structure of SIV (right). Disulfide separations for each of the mutations in the CD4-bound and unliganded structure were calculated and are given in Table 3 below.

FIG. 4 is tabulated date and plots of neutralization data obtained from rabbits immunized with four prime cycles of BSA or the indicated gp120. FIGS. 4A and 4B are tables showing the percent neutralization of the indicated viruses by sera obtained from rabbits immunized with the indicated stabilized forms of gp120, followed by immunization with a stabilized gp140 trimer. FIG. 4C is tabulated neutralization data from sera obtained from the indicated animals. The data show the effects of various peptides on the neutralization of HIV isolate YU2.SG3. This data demonstrates that the YU V3 peptide blocks neutralization of HIV isolate YU2.SG3 by antibodies produced by the boost prime immunization scheme described in Example 5. FIGS. 4D-4M are graphical representations of the data shown in FIG. 4C.

FIG. 5 is a computer generated image of the modeled structure of an HIV-1 gp120 core with V3 as defined by the coordinates in Table 2. The crystal structure of core gp120 with an intact V3 is shown bound to the membrane-distal two domains of the CD4 receptor and the Fab portion of the X5 antibody. In this orientation, the viral membrane would be positioned toward the top of the page and the target cell toward the bottom.

FIG. 6 is an alignment of the V3 sequence from the indicated HIV strains and clades and computer generated images of the structures of the V3 loop as set forth in Table 2. FIG. 6(A) V3 sequence. The sequences of JR-FL (SEQ ID NO: 21) and HXBc2 (SEQ ID NO: 22) are shown along with the consensus sequence of clades A (SEQ ID NO: 23), B (SEQ ID NO: 24), and C (SEQ ID NO: 25). For the consensus sequences, absolutely conserved residues are shown in uppercase, with variable residues in lowercase. Single letter amino acid abbreviations: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; Y, Tyr. The conserved (Arg-Pro) and (Gly-Pro-Gly-Arg) motifs indicated in grey FIG. 6(D) and FIG. 6(E). FIG. 6(B) V3 electron density and B values. 2Fobs-Fcalc density is shown for the entire V3 region and contoured at 1 s. FIG. 6(C) V3 structure. The entire V3 is shown. Regions corresponding to the fixed base, accordion-like stem, and b-hairpin tip are labeled. FIG. 6(D) Close-up view of the V3 base. From its N terminus (Cys296), V3 extends the antiparallel sheet on the outer domain of gp120. After hydrogen bonding for three residues, additional sheet contacts are interrupted by two conserved residues: Arg298, whose side-chain hydrogen bonds to three carbonyl oxygens, including two on the neighboring outer domain strand; and Pro299, which initiates the separation of outgoing and returning V3 strands. In the returning strand, antiparallel b-sheet interactions with core gp120 recommence with the carbonyl of residue 297 and continue to the disulfide at Cys331. Main-chain atoms are shown for the core and V3 base. Hydrogen bonds are depicted with dashed lines, with select distances in Å. All atoms of the highly conserved Arg298, Pro299, and Cys296-Cys331 disulfide are shown, with Arg and Pro carbons highlighted in yellow and disulfide in orange. FIG. 6(E) Conformation of the V3 tip. From Ser306 to Gly312, the main chain assumes a standard b-conformation, which terminates in a Gly-Pro-Gly-Arg b-turn (residues 312 to 315). After the turn, the returning density is less well defined, indicative of some disorder. All atoms of the tip are colored as in FIG. 6(C), with carbon atoms of the conserved tip highlighted in green. Hydrogen bonds that stabilize the β hairpin are shown as in FIG. 6(D).

FIG. 7 is a computer generated image of a modeled gp120 trimer and a coreceptor schematic. FIG. 7(A) V3 in the context of a trimer at the target cell surface. The structure of the CD4-triggered gp120 with V3 was superimposed onto the structure of four-domain CD4 and the trimer model obtained by quantification of surface parameters. In this orientation, the target cell membrane and coreceptor are expected to be positioned toward the bottom of the page. FIG. 7(B) Schematic of coreceptor interaction. CCR5 is shown with its tyrosine-sulfated N terminus (at residues 3, 10, 14, and 15) and three extracellular loops (ECLs). V3 is shown with its conserved base interacting with the sulfated CCR5 N terminus and its flexible legs allowing its conserved V3 tip to reach the second ECL of CCR5.

FIG. 8 is a set of computer generated images modeling of the V3 loop bound to the indicated antibodies. The images show the configuration of the loops and the accessibility of V3 to neutralizing antibodies. The molecular surfaces of neutralizing antibodies that block coreceptor binding are shown superimposed onto gp120 in the context of V3; antibodies 17b and X5 bind to the conserved coreceptor binding site on the core, whereas monoclonal antibodies 50.1, 58.2, 59.1, 83.1, and 447-52D bind to V3. FIG. 8(A) Superposition of V3 structures. Core with V3 is shown with V3 peptides as extracted from peptide-anti-V3 neutralizing antibody complexes after superposition of the conserved V3 tip. FIG. 8(B) Antibody accessibility of V3. Core gp120 with V3 (ribbon representation) is shown in two perpendicular views with Fab fragments (molecular surface representation) of antibodies that bind at the coreceptor binding site on either core or V3. V3 is completely surrounded by neutralizing antibodies, suggesting a high degree of accessibility for generating an immune response.

FIG. 9 is a set of computer generated images demonstrating the induced fit of the X5 CDR H3 loop. FIG. 9(A) Bound X5 structure. A stereo depiction is shown for all atoms of the CDR H3 loop of X5. Electron density (Fo−Fc, 3σ) is shown for the loop after simulated annealing to remove model bias. FIG. 9(B) Free versus bound conformations of X5. Stereo depictions of the Cα-traces are shown for the two conformations of the free X5 and of the X5 in the final refined structure of the complex with the V3-containing gp120 core. Cα-shifts are shown, with the 17 Å shift of Gly 100H labeled. (C) Same as (B), but rotated by 90°; dotted lines connect equivalent amino acids of free and bound X5.

FIG. 10 is a set of computer generated images and bar graphs showing the analysis of coreceptor binding to gp120. FIG. 10(A) Surface chemistry. The gp120 core with V3 is shown in three orientations. The middle row shows an orientation similar to that in FIGS. 5 and 6, an orientation in which the “outer” face of the V3 loop is closest to the viewer. The top row is rotated 180° about a vertical axis (showing the “inner” or core-proximal face) and the bottom row is rotated 90° about a horizontal axis. In the first column, a ribbon diagram shows gp120 colored in grey and V3 in red. The next columns represent the surface of gp120 and V3 color-coded according to the properties of the underlying atoms. Column 2 shows the molecular surface colored according to the sequence variability of the underlying amino acids for Clade B, with variable regions in purple and conserved regions in white. Columns 3 and 4 show the mutational effect of varying amino acids on CCR5 binding (column 3) or on the binding of sulfated CCR5 Nterminal peptides (column 4). Black defines surfaces that were not tested, yellow regions that when altered do not affect binding, and green areas where alterations significantly affect binding. Column 5 depicts the electrostatic potential at the solvent accessible surface, with blue showing electropositive, red electronegative, and white apolar. Column 6 depicts the gp120 surface with modeled N-linked glycans [(Nacetylglucosamine) 2(mannose)₃ cores] in orange-yellow, with the 301 glycan highlighted in purple. The molecular surface corresponding to positions “11” and “25”, suggested to be important in distinguishing between CXCR4 and CCR5, are highlighted, as well as residue 440 which sequence analysis indicates is also of some significance in this regard. FIG. 10(B) V3 sequence variation. The sequence variation was quantified (see methods) and is expressed as an entropy score: a score of zero indicates absolute conservation, a score of 4.4 indicates complete randomness. The V3 in B clade viruses which use CCR5 is comparable in terms of overall variation with other regions of gp120. The median entropy of each position within V3 is 0.21, and the interquartile range is 0-0.59. If one excludes the named variable domains, the rest of gp120 has a median entropy of 0.2, with an interquartile range of 0.-0.44. There is no statistical difference between these two distributions (Wilcoxon rank-sum p value=0.14). In contrast, V1, V2, V4 and V5 are much more variable (median entropy=1.24, interquartile range 0.67-1.70, p value compared to V3, <10-9.) Graphed in red and blue, respectively, are the position-dependent entropy score from 242 CCR5-using isolates (R5) and 47 CXCR4-using isolates (X4). Twenty positions were found to be significantly more variable in X4 than R5 viruses after correction for multiple tests. In particular, the N-linked glycoslation site (NNT) is highly conserved in R5 viruses, with 238/242 viruses reported to be R5 in the Los Alamos database carrying the potential glycosylation site at position 301, whereas only 17/47 X4 viruses retain the site (p<<10-10). This glycan has been previously observed to influence overall neutralization sensitivity. Finally, insertions were found with higher frequency in X4 viruses. The consensus R5 and X4 sequences are shown. The entropy scores from 64 R5 and 19 X4 Clade B isolates are shown, along with the respective consensus sequences. Asterisks denote where the consensus X4 sequence is the same as the consensus R5 sequence.

FIG. 11 is a set of computer generated images that show the alignment of V3 peptide:antibody structures with V3 in the context of core gp120. FIG. 11(A) X-ray structures. The structures of V3 are shown either in the context of core gp120 or bound to antibody 50.1, 447-52D, 59.1, 83.1, or 58.2. FIG. 11(B) Nuclear magnetic resonance (NMR) structures. The NMR ensembles are shown for free V3), as well as for V3 peptides bound to antibodies, 0.5β and 447-52D. All structures are aligned with the conserved Pro-Gly of the tip.

FIG. 12 is a set of computer generated images showing the modeled structure of the V1/2 for HXBc2 9c mutant.

FIG. 13 is an alignment of the amino acid sequences of the HXBc2 core (SEQ ID NO: 20) with the New HXBc2 9c (SEQ ID NO: 1).

FIG. 14 are nucleotide sequences that encode HXBc2 gp120 WT and stabilized forms thereof. FIG. 14A is a nucleotide sequence of gp120 HXBc2 DM (SEQ ID NO: 3), a nucleotide sequence of gp120 HXBc2 Core4a (SEQ ID NO: 4), and a nucleotide sequence of gp120 HXBc2 Core 4b (SEQ ID NO: 5). FIG. 14B is a nucleotide sequence of gp120 HXBc2 Core4c (SEQ ID NO: 6), a nucleotide sequence of gp120 HXBc2 Core6c (SEQ ID NO: 7), and a nucleotide sequence of gp120 HXBc2 Core6b (SEQ ID NO: 8). FIG. 14C is a nucleotide sequence of gp120 HXBc2 Core8a (SEQ ID NO: 9), a nucleotide sequence of gp120 HXBc2 Core8b (SEQ ID NO: 10), and a nucleotide sequence of gp120 HXBc2 Core8c (SEQ ID NO: 11). FIG. 14D is a nucleotide sequence of gp120 HXBc2 Core9a (SEQ ID NO: 12), a nucleotide sequence of gp120 HXBc2 Core9b (SEQ ID NO: 13), and a nucleotide sequence of gp120 HXBc2 Core9c (SEQ ID NO: 14). FIG. 14E is a nucleotide sequence of gp120 HXBc2 Core10a (SEQ ID NO: 15), a nucleotide sequence of gp120 HxBc2 Core10b (SEQ ID NO: 16), and a nucleotide sequence of gp120 HXBc2 Core10c (SEQ ID NO: 17). FIG. 14F is a nucleotide sequence of gp120 HXBc2 Core11a (SEQ ID NO: 18), a nucleotide sequence of wild type (WT) gp120 HXBc2 (SEQ ID NO: 19), and a nucleotide sequence of gp120 HXBc2 Core New 9c (SEQ ID NO: 26).

FIG. 15 is an example of an isothermal titration calorimetry curve for the binding of a soluble form of CD4 to a gp120 polypeptide. Thermodynamic properties describing this molecular interaction can be extracted from such a curve. The table shows the extracted thermodynamic parameters of a selected set of gp120 polypeptides binding to a soluble form of gp120. The collection of such data and the extraction thermodynamic parameters is well known in the art.

FIG. 16 is a set a plots of neutralization data for various HIV isolates in the presence and absence of CD4, showing the effect of CD4 triggering on viral neutralization. FIG. 16A is a bar graph showing the percent neutralization by sCD4 triggering of the V3 loop epitope. Data shown are percent neutralization of pseudovirus YU2 by the monoclonal antibodies (mAb) or sera listed under each set of bar graphs. The white bar shows neutralization by sCD4 alone. The first hatched bar shows neutralization by the specified antibody alone. The second hatched bar shows the calculated (expected) neutralization by a combination of sCD4 and the specified antibody. The stippled bar shows the observed (actual) neutralization by the combination of sCD4 and the specified antibody. 447 and 39F are anti-V3 mAbs. 17b is a mAb to the co-receptor binding site. 82-2 is an individual guinea pig sera derived from immunization with dCFIdV12 (BaL). 9427 is an individual baboon sera derived from immunization with gp140GCN-4 (YU2). FIG. 16B is a bar graph of the actual luciferase (RLU) data plotted in FIG. 16A. The figure legend describes each bar. The antibodies and sera used are as described for FIG. 16A. FIG. 16C is a bar graph of the actual luciferase (RLU) data for HIV strain JRFL. The antibodies tested are indicated. FIG. 16D is a line graph shows percent neutralization of mAb 447 with the indicated amount of sCD4 present (x-axis), calculated after affect of sCD4 is taken into account. The diamonds (♦) show the affect of sCD4 alone. The circles (●) show the combined effect of sCD4 plus mAb 447. The diamonds (♦) show the percent neutralization calculated based on the level of virus entry with sCD4 present. FIG. 16E is a line graph of the neutralization of JRFL by two guinea pig sera as shown (▴, ▪). The diamonds (♦) show the effect of sCD4 alone. The line graphs show the neutralization of each sera, calculated based on the virus entry with sCD4 present. FIG. 16F is a line graph of the neutralization of YU2 by mAbs 447, 17b, and 39F. FIG. 16G is a line graph of the neutralization of YU2 by the two animal sera that were described in FIG. 16A. FIG. 16H is a line graph of the neutralization of virus 6535 by mAbs 447 and 17b. FIG. 16I is a line graph of the neutralization of virus 6535 by two guinea pig sera as shown (♦, ▪). The diamonds (▴) show the effect of sCD4 alone. FIG. 16J is a line graph of the neutralization of virus ADA by mAbs 447. FIG. 16K is a line graph of the neutralization of virus ADA by two guinea pig sera as shown (♦, ▪). FIG. 16L is a line graph of the neutralization of the clade C virus TV1 by mAbs 447 and 17b. FIG. 16M is a line graph of the neutralization of the clade C virus TV1 by guinea pig sera derived from animals immunized with clade C dCFI Env. FIG. 16N is a line graph of the neutralization of the clade C virus ZA12 by mAb 17b. FIG. 16O is a line graph of the neutralization of the clade C virus ZA12 by guinea pig sera derived from animals immunized with clade C dCFI Env. FIG. 16P is a line graph of the neutralization of the clade C virus Z109 by mAbs 447 and 17b. FIG. 16Q is a line graph of the neutralization of the clade C virus Z109 by guinea pig sera derived from animals immunized with clade C dCFI Env.

SEQUENCE LISTING AND NOMENCLATURE

The nucleic and amino acid sequences listed in the accompanying sequence listing are shown using standard letter abbreviations for nucleotide bases, and three letter code for amino acids, as defined in 37 C.F.R. 1.822. Only one strand of each nucleic acid sequence is shown, but the complementary strand is understood as included by any reference to the displayed strand.

-   SEQ ID NO: 1 is the amino acid sequence of gp120 HXBc2 Core New 9c. -   SEQ ID NO: 2 the amino acid sequence of the gp120 with an extended     V3 loop. -   SEQ ID NO: 3 is a nucleotide sequence of gp120 HXBc2 DM. -   SEQ ID NOs: 4-18 are nucleotide sequences of stabilized HXBc2 Core     gp120. -   SEQ ID NO: 19 is a nucleotide sequence of wild type (WT) HXBc2. -   SEQ ID NO: 20 is the amino acid sequence of wild type (WT) HXBc2. -   SEQ ID NO: 21-25 are amino acid sequences of V3 loops. -   SEQ ID NO: 26 is a nucleotide sequence of gp120 HXBc2 Core New 9c. -   SEQ ID NO: 27 is the amino acid sequence of gp120 HXB2CG.     Nomenclature Conversion for Conformationally Stabilized Hxbc2     Mutants

Mutant location M95W T257S W96C I109C T123C K231C K231C Mutant Name New name S375W A433M V275C Q428C G431C E267C E268C WT core WT core C2 C3 C1S1 S2 S3 S4 S5 2a C2 x 4-0 C2S5 x x 4a C2S2 x x 4b C2S4 x x 4c C2S3 x x 5mut C12S1 x x 6a C123S1 x x x 6b C2S24 x x x 8a C123S14 x x x x 8b C123S12 x x x x 9a C23S234 x x x x x 8c C2S234 x x x x 10a C123S124 x x x x x 9b C12S134 x x x x 10c C123S134 x x x x x 9c C12S123 x x x x 10b C123S123 x x x x x 11a C12S1234 x x x x x

DETAILED DESCRIPTION

I. Terms

Unless otherwise noted, technical terms are used according to conventional usage. Definitions of common terms in molecular biology can be found in Benjamin Lewin, Genes V, published by Oxford University Press, 1994 (ISBN 0-19-854287-9); Kendrew et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0-632-02182-9); and Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8). Terms describing protein structure and structural elements of proteins can be found in Creighton, Proteins, Structures and Molecular Properties, W.H. Freeman & Co., New York, 1993 (ISBN 0-717-7030) which is incorporated by reference herein in its entirety.

Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise. Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise. It is further to be understood that all base sizes or amino acid sizes, and all molecular weight or molecular mass values, given for nucleic acids or polypeptides are approximate, and are provided for description. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The term “comprises” means “includes.” The abbreviation, “e.g.” is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation “e.g.” is synonymous with the term “for example.”

All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including explanations of terms, will control. In addition, all the materials, methods, and examples are illustrative and not intended to be limiting. In order to facilitate review of the various embodiments of the disclosure, the following explanations of specific terms are provided:

Adjuvant: A vehicle used to enhance antigenicity; such as a suspension of minerals (alum, aluminum hydroxide, aluminum phosphate) on which antigen is adsorbed; or water-in-oil emulsion in which antigen solution is emulsified in oil (MF-59, Freund's incomplete adjuvant), sometimes with the inclusion of killed mycobacteria (Freund's complete adjuvant) to further enhance antigenicity (inhibits degradation of antigen and/or causes influx of macrophages). Adjuvants also include immunostimulatory molecules, such as cytokines, costimulatory molecules, and for example, immunostimulatory DNA or RNA molecules, such as CpG oligonucleotides.

Administration: The introduction of a composition into a subject by a chosen route. For example, if the chosen route is intravenous, the composition is administered by introducing the composition into a vein of the subject.

Antibody: A polypeptide substantially encoded by an immunoglobulin gene or immunoglobulin genes, or fragments thereof, which specifically binds and recognizes an analyte (antigen) such as gp120 or an antigenic fragment of gp120. Immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as the myriad immunoglobulin variable region genes.

Antibodies exist, for example as intact immunoglobulins and as a number of well characterized fragments produced by digestion with various peptidases. For instance, Fabs, Fvs, and single-chain Fvs (SCFvs) that bind to gp120 or fragments of gp120 would be gp120-specific binding agents. This includes intact immunoglobulins and the variants and portions of them well known in the art, such as Fab′ fragments, F(ab)′₂ fragments, single chain Fv proteins (“scFv”), and disulfide stabilized Fv proteins (“dsFv”). A scFv protein is a fusion protein in which a light chain variable region of an immunoglobulin and a heavy chain variable region of an immunoglobulin are bound by a linker, while in dsFvs, the chains have been mutated to introduce a disulfide bond to stabilize the association of the chains. The term also includes genetically engineered forms such as chimeric antibodies (such as humanized murine antibodies), heteroconjugate antibodies such as bispecific antibodies). See also, Pierce Catalog and Handbook, 1994-1995 (Pierce Chemical Co., Rockford, Ill.); Kuby, J., Immunology, 3^(rd) Ed., W.H. Freeman & Co., New York, 1997.

Antibody fragments are defined as follows: (1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule produced by digestion of whole antibody with the enzyme papain to yield an intact light chain and a portion of one heavy chain; (2) Fab′, the fragment of an antibody molecule obtained by treating whole antibody with pepsin, followed by reduction, to yield an intact light chain and a portion of the heavy chain; two Fab′ fragments are obtained per antibody molecule; (3) (Fab′)₂, the fragment of the antibody obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; (4) F(ab′)2, a dimer of two Fab′ fragments held together by two disulfide bonds; (5) Fv, a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and (6) single chain antibody (“SCA”), a genetically engineered molecule containing the variable region of the light chain, the variable region of the heavy chain, linked by a suitable polypeptide linker as a genetically fused single chain molecule. The term “antibody,” as used herein, also includes antibody fragments either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA methodologies.

Typically, a naturally occurring immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. There are two types of light chain, lambda (λ) and kappa (κ). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE.

Each heavy and light chain contains a constant region and a variable region, (the regions are also known as “domains”). In combination, the heavy and the light chain variable regions specifically bind the antigen. Light and heavy chain variable regions contain a “framework” region interrupted by three hypervariable regions, also called “complementarity-determining regions” or “CDRs.” The extent of the framework region and CDRs have been defined (see, Kabat et al., Sequences of Proteins of Immunological Interest, U.S. Department of Health and Human Services, 1991, which is hereby incorporated by reference). The Kabat database is now maintained online. The sequences of the framework regions of different light or heavy chains are relatively conserved within a species. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, serves to position and align the CDRs in three-dimensional space.

The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. Thus, a V_(H) CDR3 is located in the variable domain of the heavy chain of the antibody in which it is found, whereas a V_(L) CDR1 is the CDR1 from the variable domain of the light chain of the antibody in which it is found. Light chain CDRs are sometimes referred to as CDR L1, CDR L2, and CDR L3. Heavy chain CDRs are sometimes referred to as CDR H1, CDR H2, and CDR H3.

References to “V_(H)” or “VH” refer to the variable region of an immunoglobulin heavy chain, including that of an Fv, scFv, dsFv or Fab. References to “V_(L)” or “VL” refer to the variable region of an immunoglobulin light chain, including that of an Fv, scFv, dsFv or Fab.

A “monoclonal antibody” is an antibody produced by a single clone of B-lymphocytes or by a cell into which the light and heavy chain genes of a single antibody have been transfected. Monoclonal antibodies are produced by methods known to those of skill in the art, for instance by making hybrid antibody-forming cells from a fusion of myeloma cells with immune spleen cells. These fused cells and their progeny are termed “hybridomas.” Monoclonal antibodies include humanized monoclonal antibodies.

A “humanized” immunoglobulin is an immunoglobulin including a human framework region and one or more CDRs from a non-human (such as a mouse, rat, or synthetic) immunoglobulin. The non-human immunoglobulin providing the CDRs is termed a “donor,” and the human immunoglobulin providing the framework is termed an “acceptor.” In one embodiment, all the CDRs are from the donor immunoglobulin in a humanized immunoglobulin. Constant regions need not be present, but if they are, they must be substantially identical to human immunoglobulin constant regions, such as at least about 85-90%, such as about 95% or more identical. Hence, all parts of a humanized immunoglobulin, except possibly the CDRs, are substantially identical to corresponding parts of natural human immunoglobulin sequences. A “humanized antibody” is an antibody comprising a humanized light chain and a humanized heavy chain immunoglobulin. A humanized antibody binds to the same antigen as the donor antibody that provides the CDRs. The acceptor framework of a humanized immunoglobulin or antibody may have a limited number of substitutions by amino acids taken from the donor framework. Humanized or other monoclonal antibodies can have additional conservative amino acid substitutions which have substantially no effect on antigen binding or other immunoglobulin functions. Humanized immunoglobulins can be constructed by means of genetic engineering (for example, see U.S. Pat. No. 5,585,089).

Antigenic gp120 polypeptide: An “antigenic gp120 polypeptide” includes a gp120 molecule or a portion thereof that is capable of provoking an immune response in a mammal, such as a mammal with or without an HIV infection. Administration of an antigenic gp120 polypeptide that provokes an immune response preferably leads to protective immunity against HIV.

Antigenic surface: A surface of a molecule, for example a protein such as a gp120 protein or polypeptide, capable of eliciting an immune response. An antigenic surface includes the defining features of that surface, for example the three-dimensional shape and the surface charge. An antigenic surface includes both surfaces that occur on gp120 polypeptides as well as surfaces of compounds that mimic the surface of a gp120 polypeptide (mimetics).

CD4: Cluster of differentiation factor 4 polypeptide, a T-cell surface protein that mediates interaction with the MHC class II molecule. CD4 also serves as the primary receptor site for HIV on T-cells during HIV-1 infection.

The known sequence of the CD4 precursor has a hydrophobic signal peptide, an extracellular region of approximately 370 amino acids, a highly hydrophobic stretch with significant identity to the membrane-spanning domain of the class II MHC beta chain, and a highly charged intracellular sequence of 40 resides (Maddon, Cell 42:93, 1985).

The term “CD4” includes polypeptide molecules that are derived from CD4 include fragments of CD4, generated either by chemical (for example enzymatic) digestion or genetic engineering means. Such a fragment may be one or more entire CD4 protein domains. The extracellular domain of CD4 consists of four contiguous immunoglobulin-like regions (D1, D2, D3, and D4, see Sakihama et al., Proc. Natl. Acad. Sci. 92:6444, 1995; U.S. Pat. No. 6,117,655), and amino acids 1 to 183 have been shown to be involved in gp120 binding. For instance, a binding molecule or binding domain derived from CD4 would comprise a sufficient portion of the CD4 protein to mediate specific and functional interaction between the binding fragment and a native or viral binding site of CD4. One such binding fragment includes both the D1 and D2 extracellular domains of CD4 (D1D2 is also a fragment of soluble CD4 or sCD4 which is comprised of D1D2 D3 and D4), although smaller fragments may also provide specific and functional CD4-like binding. The gp120-binding site has been mapped to D1 of CD4.

CD4 polypeptides also include “CD4-derived molecules” which encompasses analogs (non-protein organic molecules), derivatives (chemically functionalized protein molecules obtained starting with the disclosed protein sequences) or mimetics (three-dimensionally similar chemicals) of the native CD4 structure, as well as proteins sequence variants or genetic alleles that maintain the ability to functionally bind to a target molecule.

CD4BS antibodies: Antibodies that bind to or substantially overlap the CD4 binding surface of a gp120 polypeptide. The antibodies interfere with or prevent CD4 from binding to a gp120 polypeptide.

CD4i antibodies: Antibodies that bind to a conformation of gp120 induced by CD4 binding.

Contacting: Placement in direct physical association; includes both in solid and liquid form.

Computer readable media: Any medium or media, which can be read and accessed directly by a computer, so that the media is suitable for use in a computer system. Such media include, but are not limited to: magnetic storage media such as floppy discs, hard disc storage medium and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.

Computer system: Hardware that can be used to analyze atomic coordinate data. The minimum hardware of a computer-based system typically comprises a central processing unit (CPU), an input device, for example a mouse, keyboard, and the like, an output device, and a data storage device. Desirably a monitor is provided to visualize structure data. The data storage device may be RAM or other means for accessing computer readable. Examples of such systems are microcomputer workstations available from Silicon Graphics Incorporated and Sun Microsystems running Unix based Windows NT or IBM OS/2 operating systems.

Degenerate variant and conservative variant: A polynucleotide encoding a polypeptide or an antibody that includes a sequence that is degenerate as a result of the genetic code. For example, a polynucleotide encoding a gp120 polypeptide or an antibody that binds gp120 that includes a sequence that is degenerate as a result of the genetic code. There are 20 natural amino acids, most of which are specified by more than one codon. Therefore, all degenerate nucleotide sequences are included as long as the amino acid sequence of the gp120 polypeptide or antibody that binds gp120 encoded by the nucleotide sequence is unchanged. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode any given polypeptide. For instance, the codons CGU, CGC, CGA, CGG, AGA, and AGG all encode the amino acid arginine. Thus, at every position where an arginine is specified within a protein encoding sequence, the codon can be altered to any of the corresponding codons described without altering the encoded protein. Such nucleic acid variations are “silent variations,” which are one species of conservative variations. Each nucleic acid sequence herein that encodes a polypeptide also describes every possible silent variation. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine) can be modified to yield a functionally identical molecule by standard techniques. Accordingly, each “silent variation” of a nucleic acid which encodes a polypeptide is implicit in each described sequence.

Furthermore, one of ordinary skill will recognize that individual substitutions, deletions or additions which alter, add or delete a single amino acid or a small percentage of amino acids (for instance less than 5%, in some embodiments less than 1%) in an encoded sequence are conservative variations where the alterations result in the substitution of an amino acid with a chemically similar amino acid.

Conservative amino acid substitutions providing functionally similar amino acids are well known in the art. The following six groups each contain amino acids that are conservative substitutions for one another:

1) Alanine (A), Serine (S), Threonine (T);

2) Aspartic acid (D), Glutamic acid (E);

3) Asparagine (N), Glutamine (Q);

4) Arginine (R), Lysine (K);

5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and

6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W).

Not all residue positions within a protein will tolerate an otherwise “conservative” substitution. For instance, if an amino acid residue is essential for a function of the protein, even an otherwise conservative substitution may disrupt that activity.

Epitope: An antigenic determinant. These are particular chemical groups or peptide sequences on a molecule that are antigenic, such that they elicit a specific immune response. An antibody binds a particular antigenic epitope, such as an epitope of a gp120 polypeptide.

Expression: Translation of a nucleic acid into a protein. Proteins may be expressed and remain intracellular, become a component of the cell surface membrane, or be secreted into the extracellular matrix or medium.

Expression Control Sequences: Nucleic acid sequences that regulate the expression of a heterologous nucleic acid sequence to which it is operatively linked. Expression control sequences are operatively linked to a nucleic acid sequence when the expression control sequences control and regulate the transcription and, as appropriate, translation of the nucleic acid sequence. Thus expression control sequences can include appropriate promoters, enhancers, transcription terminators, a start codon (ATG) in front of a protein-encoding gene, splicing signal for introns, maintenance of the correct reading frame of that gene to permit proper translation of mRNA, and stop codons. The term “control sequences” is intended to include, at a minimum, components whose presence can influence expression, and can also include additional components whose presence is advantageous, for example, leader sequences and fusion partner sequences. Expression control sequences can include a promoter.

A promoter is a minimal sequence sufficient to direct transcription. Also included are those promoter elements which are sufficient to render promoter-dependent gene expression controllable for cell-type specific, tissue-specific, or inducible by external signals or agents; such elements may be located in the 5′ or 3′ regions of the gene. Both constitutive and inducible promoters are included (see for example, Bitter et al., Methods in Enzymology 153:516-544, 1987). For example, when cloning in bacterial systems, inducible promoters such as pL of bacteriophage lambda, plac, ptrp, ptac (ptrp-lac hybrid promoter) and the like may be used. In one embodiment, when cloning in mammalian cell systems, promoters derived from the genome of mammalian cells (such as metallothionein promoter) or from mammalian viruses (such as the retrovirus long terminal repeat; the adenovirus late promoter; the vaccinia virus 7.5K promoter) can be used. Promoters produced by recombinant DNA or synthetic techniques may also be used to provide for transcription of the nucleic acid sequences.

A polynucleotide can be inserted into an expression vector that contains a promoter sequence which facilitates the efficient transcription of the inserted genetic sequence of the host. The expression vector typically contains an origin of replication, a promoter, as well as specific nucleic acid sequences that allow phenotypic selection of the transformed cells.

gp120: The envelope protein from Human Immunodeficiency Virus (HIV). The envelope protein is initially synthesized as a longer precursor protein of 845-870 amino acids in size, designated gp160. Gp160 forms a homotrimer and undergoes glycosylation within the Golgi apparatus. It is then cleaved by a cellular protease into gp120 and gp41. Gp41 contains a transmembrane domain and remains in a trimeric configuration; it interacts with gp120 in a non-covalent manner. Gp120 contains most of the external, surface-exposed, domains of the envelope glycoprotein complex, and it is gp120 which binds both to the cellular CD4 receptor and to the cellular chemokine receptors (such as CCR5).

The mature gp120 wildtype polypeptides have about 500 amino acids in the primary sequence. Gp120 is heavily N-glycosylated giving rise to an apparent molecular weight of 120 kD. The polypeptide is comprised of five conserved regions (C1-C5) and five regions of high variability (V1-V5). Exemplary sequence of wt gp160 polypeptides are shown on GENBANK, for example accession numbers AAB05604 and AAD12142

The gp120 core has a unique molecular structure, which comprises two domains: an “inner” domain (which faces gp41) and an “outer” domain (which is mostly exposed on the surface of the oligomeric envelope glycoprotein complex). The two gp120 domains are separated by a “bridging sheet” that is not part of either domain. The gp120 core comprises 25 beta strands, 5 alpha helices, and 10 defined loop segments.

“Stabilized gp120” is a form of gp120 polypeptide from HIV-1, characterized by an increase in T_(m) over the wild type gp120. In some examples the gp120 is stabilized by the replacement of at least two amino acids of gp120 with cysteines such that a disulfide bond can form, wherein the gp120 protein has a T_(m) of greater than about 53.8° C. The stabilized gp120 mutants may contain amino acid substitutions that fill cavities present in the core of native gp120. The stabilized gp120 can bind CD4. Stabilized forms of gp120 may include forms that have synthetic amino acids. Several exemplary stabilized gp120 proteins are disclosed herein.

Gp120 polypeptides also include “gp120-derived molecules” which encompasses analogs (non-protein organic molecules), derivatives (chemically functionalized protein molecules obtained starting with the disclosed protein sequences) or mimetics (three-dimensionally similar chemicals) of the native gp120 structure, as well as proteins sequence variants (such as mutants), genetic alleles, fusions proteins of gp120, or combinations thereof.

The third variable region referred to herein as the V3 loop is a loop of about 35 amino acids critical for the binding of the co-receptor and determination of which of the co-receptors will bind. In certain examples the V3 loop comprises residues 296-331.

The numbering used in gp120 polypeptides disclosed herein is relative to the HXB2 numbering scheme as set forth in Numbering Positions in HIV Relative to HXB2CG Bette Korber et al., Human Retroviruses and AIDS 1998: A Compilation and Analysis of Nucleic Acid and Amino Acid Sequences. Korber B, Kuiken C L, Foley B, Hahn B, McCutchan F, Mellors J W, and Sodroski J, Eds. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, N. Mex. which is incorporated by reference herein in its entirety. For reference, the amino acid sequence of HXB2CG is given below as SEQ ID NO: 27: lwvtvyygvpvwkeatttlfcasdakaydtevhnvwathacvptdpnpqevvlvnvtenfnmwkndmveqmhediislwdqslkpcvkltplcvslkctdlkndtntnsssgrmimekgeiknicsfnistsirgkvqkeyaffykldiipidndttsykltscntsvitqacpkvsfepipihycapagfailkcnnktfngtgpctnvstvqcthgirpvvstqlllngslaeeevvirsvnftdnaktiivqlntsveinctrpnnntrkririqrgpgrafvtigkignmrqahcnisrakwnntlkqiasklreqfgnnktiifkqssggdpeivthsfncggeffycnstqlfnstwfnstwstegsnntegsdtitlpcrikqiinmwqkvgkamyappisgqircssnitgllltrdggnsnneseifrpgggdmrdnwrselykykyvvkieplgvaptkakarrvvqrekr (SEQ ID NO: 27). HXB2 is also known as: HXBc2, for HXB clone 2; HXB2R, in the Los Alamos HIV database, with the R for revised, as it was slightly revised relative to the original HXB2 sequence; and HXB2CG in GenBank, for HXB2 complete genome.

Heavy atom derivatization: A method of producing a chemically modified form of a protein crystal, for example a crystal containing gp120. In practice, a crystal is soaked in a solution containing heavy metal atom salts, or organometallic compounds, such as lead chloride, gold thiomalate, thimerosal or uranyl acetate, which can diffuse through the solvent channels of the crystal and bind the surface of the protein. The location(s) of the bound heavy metal atom(s) can be determined by X-ray diffraction analysis of the soaked crystal. This information, in turn, is used to generate the phase information used to construct three-dimensional structure of the enzyme (see Blundel and Johnson, Protein Crystallography, Academic Press (1976).

Host cells: Cells in which a vector can be propagated and its DNA expressed. The cell may be prokaryotic or eukaryotic. The term also includes any progeny of the subject host cell. It is understood that all progeny may not be identical to the parental cell since there may be mutations that occur during replication. However, such progeny are included when the term “host cell” is used.

In silico: A process performed virtually within a computer. For example, using a computer, a virtual compound can be screened for surface similarity or conversely surface complementarity to a virtual representation of the atomic positions at least a portion of a gp120 polypeptide, for example as stabilized gp120, such as defined in Table 1 or a gp120 with an extended V3 loop, such as defined in Table 2.

Immune response: A response of a cell of the immune system, such as a B cell, T cell, or monocyte, to a stimulus. In one embodiment, the response is specific for a particular antigen (an “antigen-specific response”). In one embodiment, an immune response is a T cell response, such as a CD4+ response or a CD8+ response. In another embodiment, the response is a B cell response, and results in the production of specific antibodies.

Immunogenic peptide: A peptide which comprises an allele-specific motif or other sequence, such as an N-terminal repeat, such that the peptide will bind an MHC molecule and induce a cytotoxic T lymphocyte (“CTL”) response, or a B cell response (for example antibody production) against the antigen from which the immunogenic peptide is derived.

In one embodiment, immunogenic peptides are identified using sequence motifs or other methods, such as neural net or polynomial determinations known in the art. Typically, algorithms are used to determine the “binding threshold” of peptides to select those with scores that give them a high probability of binding at a certain affinity and will be immunogenic. The algorithms are based either on the effects on MHC binding of a particular amino acid at a particular position, the effects on antibody binding of a particular amino acid at a particular position, or the effects on binding of a particular substitution in a motif-containing peptide. Within the context of an immunogenic peptide, a “conserved residue” is one which appears in a significantly higher frequency than would be expected by random distribution at a particular position in a peptide. In one embodiment, a conserved residue is one where the MHC structure may provide a contact point with the immunogenic peptide. In one specific non-limiting example, an immunogenic polypeptide includes a region of gp120, or a fragment thereof.

Immunogenic composition: A composition comprising an immunogenic peptide that induces a measurable CTL response against virus expressing the immunogenic peptide, or induces a measurable B cell response (such as production of antibodies) against the immunogenic peptide. In one example an “immunogenic composition” is composition comprising a gp120 polypeptide that induces a measurable CTL response against virus expressing gp120 polypeptide, or induces a measurable B cell response (such as production of antibodies) against a gp120 polypeptide. It further refers to isolated nucleic acids encoding an immunogenic peptide, such as a nucleic acid that can be used to express the gp120 polypeptide (and thus be used to elicit an immune response against this polypeptide).

For in vitro use, an immunogenic composition may consist of the isolated protein, peptide epitope, or nucleic acid encoding the protein, or peptide epitope. For in vivo use, the immunogenic composition will typically comprise the protein or immunogenic peptide in pharmaceutically acceptable carriers, and/or other agents. Any particular peptide, such as a gp120 polypeptide, or nucleic acid encoding the polypeptide, can be readily tested for its ability to induce a CTL or B cell response by art-recognized assays. Immunogenic compositions can include adjuvants, which are well known to one of skill in the art.

Immunologically reactive conditions: Includes reference to conditions which allow an antibody raised against a particular epitope to bind to that epitope to a detectably greater degree than, and/or to the substantial exclusion of, binding to substantially all other epitopes. Immunologically reactive conditions are dependent upon the format of the antibody binding reaction and typically are those utilized in immunoassay protocols or those conditions encountered in vivo. The immunologically reactive conditions employed in the methods are “physiological conditions” which include reference to conditions (such as temperature, osmolarity, pH) that are typical inside a living mammal or a mammalian cell. While it is recognized that some organs are subject to extreme conditions, the intra-organismal and intracellular environment is normally about pH 7 (such as from pH 6.0 to pH 8.0, more typically pH 6.5 to 7.5), contains water as the predominant solvent, and exists at a temperature above 0° C. and below 50° C. Osmolarity is within the range that is supportive of cell viability and proliferation.

Immunotherapy: A method of evoking an immune response against a virus based on their production of target antigens. Immunotherapy based on cell-mediated immune responses involves generating a cell-mediated response to cells that produce particular antigenic determinants, while immunotherapy based on humoral immune responses involves generating specific antibodies to virus that produce particular antigenic determinants.

Inhibiting or treating a disease: Inhibiting the full development of a disease or condition, for example, in a subject who is at risk for a disease such as acquired immune deficiency syndrome (AIDS), AIDS related conditions, HIV-1 infection, or combinations thereof. “Treatment” refers to a therapeutic intervention that ameliorates a sign or symptom of a disease or pathological condition after it has begun to develop. The term “ameliorating,” with reference to a disease or pathological condition, refers to any observable beneficial effect of the treatment. The beneficial effect can be evidenced, for example, by a delayed onset of clinical symptoms of the disease in a susceptible subject, a reduction in severity of some or all clinical symptoms of the disease, a slower progression of the disease, a reduction in the number of metastases, an improvement in the overall health or well-being of the subject, or by other parameters well known in the art that are specific to the particular disease. A “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of a disease or exhibits only early signs for the purpose of decreasing the risk of developing pathology.

Isolated: An “isolated” biological component (such as a nucleic acid, peptide or protein) has been substantially separated, produced apart from, or purified away from other biological components in the cell of the organism in which the component naturally occurs, such as, other chromosomal and extrachromosomal DNA and RNA, and proteins. Nucleic acids, peptides and proteins which have been “isolated” thus include nucleic acids and proteins purified by standard purification methods. The term also embraces nucleic acids, peptides, and proteins prepared by recombinant expression in a host cell as well as chemically synthesized nucleic acids.

K_(d): The dissociation constant for a given interaction, such as a polypeptide ligand interaction. For example, for the bimolecular interaction of CD4 and gp120 it is the concentration of the individual components of the bimolecular interaction divided by the concentration of the complex.

Leukocyte: Cells in the blood, also termed “white cells,” that are involved in defending the body against infective organisms and foreign substances. Leukocytes are produced in the bone marrow. There are 5 main types of white blood cell, subdivided between 2 main groups: polymorphonuclear leukocytes (neutrophils, eosinophils, basophils) and mononuclear leukocytes (monocytes and lymphocytes).

Ligand: Any molecule which specifically binds a protein, such as a gp120 protein, and includes, inter alia, antibodies that specifically bind a gp120 protein. In alternative embodiments, the ligand is a protein or a small molecule (one with a molecular weight less than 6 kiloDaltons).

Mimetic: A molecule (such as an organic chemical compound) that mimics the activity of an agent, such as the activity of a gp120 protein, for example by inducing an immune response to gp120. Peptidomimetic and organomimetic embodiments are within the scope of this term, whereby the three-dimensional arrangement of the chemical constituents of such peptido- and organomimetics mimic the three-dimensional arrangement of the peptide backbone and component amino acid side chains in the peptide, resulting in such peptido- and organomimetics of the peptides having substantial specific activity. For computer modeling applications, a pharmacophore is an idealized, three-dimensional definition of the structural requirements for biological activity. Peptido- and organomimetics can be designed to fit each pharmacophore with computer modeling software (using computer assisted drug design or CADD). See Walters, “Computer-Assisted Modeling of Drugs”, in Klegerman & Groves, eds., 1993, Pharmaceutical Biotechnology, Interpharm Press: Buffalo Grove, Ill., pp. 165-174 and Principles of Pharmacology (ed. Munson, 1995), chapter 102 for a description of techniques used in computer assisted drug design.

Molecular Replacement: A method that involves generating a preliminary model, such as a model of a gp120 polypeptide, whose structure coordinates are unknown, by orienting and positioning a molecule whose structure coordinates are known (such as coordinates from Table 1) within the unit cell of the unknown crystal so as best to account for the observed diffraction pattern of the unknown crystal. Phases can then be calculated from this model and combined with the observed amplitudes to give an approximate Fourier synthesis of the structure whose coordinates are unknown. This, in turn, can be subject to any of the several forms of refinement to provide a final, accurate structure of the unknown molecule (see Lattman, Methods in Enzymology, 115:55-77, 1985; Rossmann, ed., “The Molecular Replacement Method”, Int. Sci. Rev. Ser., No. 13, Gordon & Breach, New York, 1972). Using the structure coordinates of gp120, such as a stabilized gp120 provided herein; molecular replacement may be used to determine the structure coordinates of a crystalline mutant or homologue of gp120, a different crystal form of gp120, or gp120 in complex with another molecule, such as an antibody, cell surface receptor, or combination thereof.

Naturally Occurring Amino Acids: L-isomers of the naturally occurring amino acids. The naturally occurring amino acids are glycine, alanine, valine, leucine, isoleucine, serine, methionine, threonine, phenylalanine, tyrosine, tryptophan, cysteine, proline, histidine, aspartic acid, asparagine, glutamic acid, glutamine, gamma.-carboxyglutamic acid, arginine, ornithine and lysine. Unless specifically indicated, all amino acids referred to in this application are in the L-form. “Synthetic amino acids” refers to amino acids that are not naturally found in proteins. Examples of synthetic amino acids used herein, include racemic mixtures of selenocysteine and selenomethionine. In addition, unnatural amino acids include the D or L forms of nor-leucine, para-nitrophenylalanine, homophenylalanine, para-fluorophenylalanine, 3-amino-2-benzylpropionic acid, homoarginine, and D-phenylalanine. The term “positively charged amino acid” refers to any naturally occurring or synthetic amino acid having a positively charged side chain under normal physiological conditions. Examples of positively charged naturally occurring amino acids are arginine, lysine and histidine. The term “negatively charged amino acid” refers to any naturally occurring or synthetic amino acid having a negatively charged side chain under normal physiological conditions. Examples of negatively charged naturally occurring amino acids are aspartic acid and glutamic acid. The term “hydrophobic amino acid” refers to any amino acid having an uncharged, nonpolar side chain that is relatively insoluble in water. Examples of naturally occurring hydrophobic amino acids are alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan and methionine. The term “hydrophilic amino acid” refers to any amino acid having an uncharged, polar side chain that is relatively soluble in water. Examples of naturally occurring hydrophilic amino acids are serine, threonine, tyrosine, asparagine, glutamine, and cysteine.

Nucleic acid: A polymer composed of nucleotide units (ribonucleotides, deoxyribonucleotides, related naturally occurring structural variants, and synthetic non-naturally occurring analogs thereof) linked via phosphodiester bonds, related naturally occurring structural variants, and synthetic non-naturally occurring analogs thereof. Thus, the term includes nucleotide polymers in which the nucleotides and the linkages between them include non-naturally occurring synthetic analogs, such as, for example and without limitation, phosphorothioates, phosphoramidates, methyl phosphonates, chiral-methyl phosphonates, 2-O-methyl ribonucleotides, peptide-nucleic acids (PNAs), and the like. Such polynucleotides can be synthesized, for example, using an automated DNA synthesizer. The term “oligonucleotide” typically refers to short polynucleotides, generally no greater than about 50 nucleotides. It will be understood that when a nucleotide sequence is represented by a DNA sequence (i.e., A, T, G, C), this also includes an RNA sequence (i.e., A, U, G, C) in which “U” replaces “T.”

“Nucleotide” includes, but is not limited to, a monomer that includes a base linked to a sugar, such as a pyrimidine, purine or synthetic analogs thereof, or a base linked to an amino acid, as in a peptide nucleic acid (PNA). A nucleotide is one monomer in a polynucleotide. A nucleotide sequence refers to the sequence of bases in a polynucleotide. A gp120 polynucleotide is a nucleic acid encoding a gp120 polypeptide.

Conventional notation is used herein to describe nucleotide sequences: the left-hand end of a single-stranded nucleotide sequence is the 5′-end; the left-hand direction of a double-stranded nucleotide sequence is referred to as the 5′-direction. The direction of 5′ to 3′ addition of nucleotides to nascent RNA transcripts is referred to as the transcription direction. The DNA strand having the same sequence as an mRNA is referred to as the “coding strand;” sequences on the DNA strand having the same sequence as an mRNA transcribed from that DNA and which are located 5′ to the 5′-end of the RNA transcript are referred to as “upstream sequences;” sequences on the DNA strand having the same sequence as the RNA and which are 3′ to the 3′ end of the coding RNA transcript are referred to as “downstream sequences.”

“cDNA” refers to a DNA that is complementary or identical to an mRNA, in either single stranded or double stranded form.

“Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (for example, rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA produced by that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and non-coding strand, used as the template for transcription, of a gene or cDNA can be referred to as encoding the protein or other product of that gene or cDNA. Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. Nucleotide sequences that encode proteins and RNA may include introns.

“Recombinant nucleic acid” refers to a nucleic acid having nucleotide sequences that are not naturally joined together. This includes nucleic acid vectors comprising an amplified or assembled nucleic acid which can be used to transform a suitable host cell. A host cell that comprises the recombinant nucleic acid is referred to as a “recombinant host cell.” The gene is then expressed in the recombinant host cell to produce, such as a “recombinant polypeptide.” A recombinant nucleic acid may serve a non-coding function (such as a promoter, origin of replication, ribosome-binding site, etc.) as well.

A first sequence is an “antisense” with respect to a second sequence if a polynucleotide whose sequence is the first sequence specifically hybridizes with a polynucleotide whose sequence is the second sequence.

Terms used to describe sequence relationships between two or more nucleotide sequences or amino acid sequences include “reference sequence,” “selected from,” “comparison window,” “identical,” “percentage of sequence identity,” “substantially identical,” “complementary,” and “substantially complementary.”

For sequence comparison of nucleic acid sequences and amino acids sequences, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters are used. Methods of alignment of sequences for comparison are well known in the art. Optimal alignment of sequences for comparison can be conducted, for example, by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482, 1981, by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443, 1970, by the search for similarity method of Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444, 1988, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by manual alignment and visual inspection (see for example, Current Protocols in Molecular Biology (Ausubel et al., eds 1995 supplement)).

One example of a useful algorithm is PILEUP, PILEUP uses a simplification of the progressive alignment method of Feng & Doolittle, J. Mol. Evol. 35:351-360, 1987. The method used is similar to the method described by Higgins & Sharp, CABIOS 5:151-153, 1989. Using PILEUP, a reference sequence is compared to other test sequences to determine the percent sequence identity relationship using the following parameters: default gap weight (3.00), default gap length weight (0.10), and weighted end gaps. PILEUP can be obtained from the GCG sequence analysis software package, such as version 7.0 (Devereaux et al., Nuc. Acids Res. 12:387-395, 1984.

Another example of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and the BLAST 2.0 algorithm, which are described in Altschul et al., J. Mol. Biol. 215:403-410, 1990 and Altschul et al., Nucleic Acids Res. 25:3389-3402, 1977. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, alignments (B) of 50, expectation (E) of 10, M=5, N=−4, and a comparison of both strands. The BLASTP program (for amino acid sequences) uses as defaults a word length (W) of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915, 1989).

Another indicia of sequence similarity between two nucleic acids is the ability to hybridize. The more similar are the sequences of the two nucleic acids, the more stringent the conditions at which they will hybridize. The stringency of hybridization conditions are sequence-dependent and are different under different environmental parameters. Thus, hybridization conditions resulting in particular degrees of stringency will vary depending upon the nature of the hybridization method of choice and the composition and length of the hybridizing nucleic acid sequences. Generally, the temperature of hybridization and the ionic strength (especially the Na⁺ and/or Mg⁺⁺ concentration) of the hybridization buffer will determine the stringency of hybridization, though wash times also influence stringency. Generally, stringent conditions are selected to be about 5° C. to 20° C. lower than the thermal melting point (T_(m)) for the specific sequence at a defined ionic strength and pH. The T_(m) is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. Conditions for nucleic acid hybridization and calculation of stringencies can be found, for example, in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 2001; Tijssen, Hybridization With Nucleic Acid Probes, Part I: Theory and Nucleic Acid Preparation, Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Ltd., NY, N.Y., 1993 and Ausubel et al. Short Protocols in Molecular Biology, 4^(th) ed., John Wiley & Sons, Inc., 1999.

“Stringent conditions” encompass conditions under which hybridization will only occur if there is less than 25% mismatch between the hybridization molecule and the target sequence. “Stringent conditions” may be broken down into particular levels of stringency for more precise definition. Thus, as used herein, “moderate stringency” conditions are those under which molecules with more than 25% sequence mismatch will not hybridize; conditions of “medium stringency” are those under which molecules with more than 15% mismatch will not hybridize, and conditions of “high stringency” are those under which sequences with more than 10% mismatch will not hybridize. Conditions of “very high stringency” are those under which sequences with more than 6% mismatch will not hybridize. In contrast nucleic acids that hybridize under “low stringency conditions include those with much less sequence identity, or with sequence identity over only short subsequences of the nucleic acid. For example, a nucleic acid construct can include a polynucleotide sequence that hybridizes under high stringency or very high stringency, or even higher stringency conditions to a polynucleotide sequence that encodes SEQ ID NO: 1.

Operably linked: A first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences are contiguous and, where necessary to join two protein-coding regions, in the same reading frame.

Peptide Modifications: The present disclosure includes mutant gp120 peptides, as well as synthetic embodiments. In addition, analogues (non-peptide organic molecules), derivatives (chemically functionalized peptide molecules obtained starting with the disclosed peptide sequences) and variants (homologs) of gp120 can be utilized in the methods described herein. The peptides disclosed herein include a sequence of amino acids that can be either L- and/or D-amino acids, naturally occurring and otherwise.

Peptides can be modified by a variety of chemical techniques to produce derivatives having essentially the same activity as the unmodified peptides, and optionally having other desirable properties. For example, carboxylic acid groups of the protein, whether carboxyl-terminal or side chain, may be provided in the form of a salt of a pharmaceutically-acceptable cation or esterified to form a C₁-C₁₆ ester, or converted to an amide of formula NR₁R₂ wherein R₁ and R₂ are each independently H or C₁-C₁₆ alkyl, or combined to form a heterocyclic ring, such as a 5- or 6-membered ring. Amino groups of the peptide, whether amino-terminal or side chain, may be in the form of a pharmaceutically-acceptable acid addition salt, such as the HCl, HBr, acetic, benzoic, toluene sulfonic, maleic, tartaric and other organic salts, or may be modified to C₁-C₁₆ alkyl or dialkyl amino or further converted to an amide.

Hydroxyl groups of the peptide side chains can be converted to C₁-C₁₆ alkoxy or to a C₁-C₁₆ ester using well-recognized techniques. Phenyl and phenolic rings of the peptide side chains can be substituted with one or more halogen atoms, such as F, Cl, Br or I, or with C₁-C₁₆ alkyl, C₁-C₁₆ alkoxy, carboxylic acids and esters thereof, or amides of such carboxylic acids. Methylene groups of the peptide side chains can be extended to homologous C₂-C₄ alkylenes. Thiols can be protected with any one of a number of well-recognized protecting groups, such as acetamide groups. Those skilled in the art will also recognize methods for introducing cyclic structures into the peptides of this disclosure to select and provide conformational constraints to the structure that result in enhanced stability. For example, a C- or N-terminal cysteine can be added to the peptide, so that when oxidized the peptide will contain a disulfide bond, generating a cyclic peptide. Other peptide cyclizing methods include the formation of thioethers and carboxyl- and amino-terminal amides and esters.

Peptidomimetic and organomimetic embodiments are also within the scope of the present disclosure, whereby the three-dimensional arrangement of the chemical constituents of such peptido- and organomimetics mimic the three-dimensional arrangement of the peptide backbone and component amino acid side chains, resulting in such peptido- and organomimetics of the proteins of this disclosure. For computer modeling applications, a pharmacophore is an idealized, three-dimensional definition of the structural requirements for biological activity. Peptido- and organomimetics can be designed to fit each pharmacophore with current computer modeling software (using computer assisted drug design or CADD). See Walters, “Computer-Assisted Modeling of Drugs”, in Klegerman & Groves, eds., 1993, Pharmaceutical Biotechnology, Interpharm Press: Buffalo Grove, Ill., pp. 165-174 and Principles of Pharmacology Munson (ed.) 1995, Ch. 102, for descriptions of techniques used in CADD. Also included within the scope of the disclosure are mimetics prepared using such techniques. In one example, a mimetic mimics the antigenic activity generated by gp120 a mutant, a variant, fragment, or fusion thereof.

Pharmaceutical agent: A chemical compound or composition capable of inducing a desired therapeutic or prophylactic effect when properly administered to a subject or a cell. “Incubating” includes a sufficient amount of time for a drug to interact with a cell. “Contacting” includes incubating a drug in solid or in liquid form with a cell. An “anti-viral agent” or “anti-viral drug” is an agent that specifically inhibits a virus from replicating or infecting cells. Similarly, an “anti-retroviral agent” is an agent that specifically inhibits a retrovirus from replicating or infecting cells.

A “therapeutically effective amount” is a quantity of a chemical composition or an anti-viral agent sufficient to achieve a desired effect in a subject being treated. For instance, this can be the amount necessary to inhibit viral replication or to measurably alter outward symptoms of the viral infection, such as increase of T cell counts in the case of an HIV-1 infection. In general, this amount will be sufficient to measurably inhibit virus (for example, HIV) replication or infectivity. When administered to a subject, a dosage will generally be used that will achieve target tissue concentrations (for example, in lymphocytes) that has been shown to achieve in vitro inhibition of viral replication.

Pharmaceutically acceptable carriers: The pharmaceutically acceptable carriers of use are conventional. Remington's Pharmaceutical Sciences, by E. W. Martin, Mack Publishing Co., Easton, Pa., 15th Edition, 1975, describes compositions and formulations suitable for pharmaceutical delivery of the fusion proteins herein disclosed.

In general, the nature of the carrier will depend on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (such as powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate.

Polypeptide: Any chain of amino acids, regardless of length or post-translational modification (such as glycosylation or phosphorylation). “Polypeptide” applies to amino acid polymers to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer as well as in which one or more amino acid residue is a non-natural amino acid, for example a artificial chemical mimetic of a corresponding naturally occurring amino acid. In one embodiment, the polypeptide is a gp120 polypeptide, such as a stabilized gp120. A “residue” refers to an amino acid or amino acid mimetic incorporated in a polypeptide by an amide bond or amide bond mimetic. A polypeptide has an amino terminal (N-terminal) end and a carboxy terminal (C-terminal) end. “Polypeptide” is used interchangeably with peptide or protein, and is used interchangeably herein to refer to a polymer of amino acid residues.

Protein core: The protein core refers to the interior of a folded protein, which is substantially free of solvent exposure, such as solvent in the form of water molecules in solution. Typically, the protein core is predominately composed of hydrophobic or apolar amino acids. In some examples, a protein core may contain charged amino acids, for example aspartic acid, glutamic acid, arginine, and/or lysine. The inclusion of uncompensated charged amino acids (a compensated charged amino can be in the form of a salt bridge) in the protein core can lead to a destabilized protein. That is, a protein with a lower T_(m) then a similar protein without an uncompensated charged amino acid in the protein core. In other examples, a protein core may have a cavity with in the protein core. Cavities are essentially voids within a folded protein where amino acids or amino acid side chains are not present. Such cavities can also destabilize a protein relative to a similar protein without a cavity. Thus, when creating a stabilized form of a protein, for example a stabilized form of gp120, it may be advantageous to substitute amino acid residues within the core in order to fill cavities present in the wild-type protein.

Purified: The term purified does not require absolute purity; rather, it is intended as a relative term. Thus, for example, a purified protein is one in which the protein is more enriched than the protein is in its natural environment within a cell. Preferably, a preparation is purified such that the protein represents at least 50% of the protein content of the preparation.

The gp120 polypeptides disclosed herein, or antibodies that specifically bind gp120, can be purified by any of the means known in the art. See for example Guide to Protein Purification, ed. Deutscher, Meth. Enzymol. 185, Academic Press, San Diego, 1990; and Scopes, Protein Purification: Principles and Practice, Springer Verlag, New York, 1982. Substantial purification denotes purification from other proteins or cellular components. A substantially purified protein is at least 60%, 70%, 80%, 90%, 95% or 98% pure. Thus, in one specific, non-limiting example, a substantially purified protein is 90% free of other proteins or cellular components.

Space Group: The arrangement of symmetry elements of a crystal.

Structure coordinates: Mathematical coordinates derived from mathematical equations related to the patterns obtained on diffraction of a monochromatic beam of X-rays by the atoms (scattering centers) such as a gp120, a gp120:CD4 complex, a gp120:antibody complex, or combinations thereof in a crystal in crystal form. The diffraction data are used to calculate an electron density map of the repeating unit of the crystal. The electron density maps are used to establish the positions of the individual atoms within the unit cell of the crystal. In one example, the term “structure coordinates” refers to Cartesian coordinates derived from mathematical equations related to the patterns obtained on diffraction of a monochromatic beam of X-rays, such as by the atoms of a stabilized form of gp120 in crystal form.

Atomic coordinate data, such as that in Table 1 and Table 2 lists each atom by a unique number (column 2); the atom name in the context of the residue to which it belongs (column 3), for example CA refers to the alpha carbon of the peptide backbone (detailed descriptions of the atom identifiers for each residue can be found for example in Creighton, Proteins, Structures and Molecular Properties, W.H. Freeman & Co., New York, 1993); the amino acid residue in which the atom is located (column 4); the chain identifier (column 4′) which may or may not be included, the number of the residue (column 5); the coordinates (for example, X, Y, Z) which define with respect to the crystallographic axes the atomic position (in Å) of the respective atom (columns 6, 7, and 8); the occupancy of the atom in the respective position (column 9); the “B-factor”, which is the isotropic displacement parameter (in Å²) and accounts for movement of the atom around its atomic center (column 10).

Those of ordinary skill in the art understand that a set of structure coordinates determined by X-ray crystallography is not without standard error. For the purpose of this disclosure, any set of structure coordinates for a stabilized form of gp120 or a gp120 with an extended V3 loop that have a root mean square deviation of protein backbone atoms (N, Cα, C and 0) of less than about 1.0 Angstroms when superimposed, such as about 0.75, or about 0.5, or about 0.25 Angstroms, using backbone atoms, on the structure coordinates listed in Table 1 or Table 2 shall (in the absence of a explicit statement to the contrary) be considered identical.

Subject: Living multi-cellular vertebrate organisms, a category that includes both human and veterinary subjects, including human and non-human mammals.

T Cell: A white blood cell critical to the immune response. T cells include, but are not limited to, CD4⁺ T cells and CD8⁺ T cells. A CD4⁺ T lymphocyte is an immune cell that carries a marker on its surface known as “cluster of differentiation 4” (CD4). These cells, also known as helper T cells, help orchestrate the immune response, including antibody responses as well as killer T cell responses. CD8⁺ T cells carry the “cluster of differentiation 8” (CD8) marker. In one embodiment, a CD8 T cells is a cytotoxic T lymphocytes. In another embodiment, a CD8 cell is a suppressor T cell.

Therapeutic agent: Used in a generic sense, it includes treating agents, prophylactic agents, and replacement agents.

T_(m): The temperature at which a change of state occurs. For example, the temperature at which gp120 undergoes a transition from the folded form to the unfolded form. Essentially this is the temperature at which the structure melts away. Stabilized gp120 has a higher T_(m) than native gp120. Another example would be the temperature at which a DNA duplex melts.

Transformed: A transformed cell is a cell into which has been introduced a nucleic acid molecule by molecular biology techniques. As used herein, the term transformation encompasses all techniques by which a nucleic acid molecule might be introduced into such a cell, including transfection with viral vectors, transformation with plasmid vectors, and introduction of DNA by electroporation, lipofection, and particle gun acceleration.

Unit Cell: The smallest building block of a crystal. The entire volume of a crystal may be constructed by regular assembly of such blocks. Each unit cell comprises a complete representation of the unit of pattern, the repetition of which builds produces a crystal lattice

Vector: A nucleic acid molecule as introduced into a host cell, thereby producing a transformed host cell. Recombinant DNA vectors are vectors having recombinant DNA. A vector can include nucleic acid sequences that permit it to replicate in a host cell, such as an origin of replication. A vector can also include one or more selectable marker genes and other genetic elements known in the art. Viral vectors are recombinant DNA vectors having at least some nucleic acid sequences derived from one or more viruses.

Virus: Microscopic infectious organism that reproduces inside living cells. A virus consists essentially of a core of a single nucleic acid surrounded by a protein coat, and has the ability to replicate only inside a living cell. “Viral replication” is the production of additional virus by the occurrence of at least one viral life cycle. A virus may subvert the host cells' normal functions, causing the cell to behave in a manner determined by the virus. For example, a viral infection may result in a cell producing a cytokine, or responding to a cytokine, when the uninfected cell does not normally do so.

“Retroviruses” are RNA viruses wherein the viral genome is RNA. When a host cell is infected with a retrovirus, the genomic RNA is reverse transcribed into a DNA intermediate which is integrated very efficiently into the chromosomal DNA of infected cells. The integrated DNA intermediate is referred to as a provirus. The term “lentivirus” is used in its conventional sense to describe a genus of viruses containing reverse transcriptase. The lentiviruses include the “immunodeficiency viruses” which include human immunodeficiency virus (HIV) type 1 and type 2 (HIV-1 and HIV-2), simian immunodeficiency virus (SIV), and feline immunodeficiency virus (FIV).

HIV-1 is a retrovirus that causes immunosuppression in humans (HIV disease), and leads to a disease complex known as the acquired immunodeficiency syndrome (AIDS). “HIV disease” refers to a well-recognized constellation of signs and symptoms (including the development of opportunistic infections) in persons who are infected by an HIV virus, as determined by antibody or western blot studies. Laboratory findings associated with this disease are a progressive decline in T cells.

X5: An antibody that bonds a conformation of gp120 induced by the binding of CD4. Antibodies that bind to gp120 in a conformation induced by CD4 binding are termed CD4i antibodies.

ΔS: The change in entropy, such as the change in entropy upon the association of gp120 and CD4 or an antibody or antibody fragment, for example X5.

ΔH: The change in the enthalpy, such as the change enthalpy upon the association of gp120 and CD4 or an antibody.

II. Overview of Several Embodiments

Provided herein in various embodiments are gp120 polypeptides, which are useful to induce immunogenic response in vertebrate animals (such as mammals, for example primates, such as humans) to lentivirus, such as SIV or HIV (for example HIV-I and HIV-II).

In several embodiments, the gp120 polypeptides are stabilized in a CD4 bound conformation. In several disclosed examples, the gp120 polypeptides are stabilized by modification. In certain examples, these modifications can be the introduction of a plurality of non-naturally occurring cross-linking cysteine residues. In certain examples, the modification can be the introduction of at least one amino acid substitution in the protein core of gp120.

In several disclosed examples, cysteines are introduced into the gp120 polypeptide at position 96, 109, 123, 231, 267, 275, 428, 431 or in combinations thereof. In some examples of gp120 polypeptides disclosed herein, the plurality of non-naturally occurring cross-linking cysteine residues are defined by the interaction and crosslinking of at least one of residue pairs 96 and 275; 109 and 428; 123 and 431; and 231 and 267. In some embodiments, all of the residue pairs 96 and 275; 109 and 428; 123 and 431; and 231 and 267 are crosslinked.

In some embodiments, the stabilized gp120 polypeptide contains one or more amino acid substitutions in the protein core. In several examples, the substitution is made at position 95, 257, 375, 433, or a combination thereof. In specific examples, the substitution is a serine to tryptophan substitution at position 95, a threonine to serine substitution at position 257, a serine to tryptophan substitution at position 375, an alanine to methionine substitution at position 433, or a combination thereof.

In specific examples, the stabilized gp120 polypeptide includes the amino acid sequence set forth as SEQ ID NO: 1 or is encoded by one of SEQ ID NO: 4, 5, 6, 7, 8, 10, 11, 12, 13, and 14, 15, 16, 17, 18, or degenerate variants thereof. In still other embodiments, the stabilized gp120 contains a portion of the amino acid sequence set forth as SED ID NO: 1 or as encoded by any one of SEQ NOs:4-18, for example, a domain such as the outer domain, or a contiguous stretch of about 5 or more amino acids, such as about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, or more amino acids.

In other examples, the gp120 polypeptide has the V3 loop in an extended conformation. In one example, the gp120 polypeptide with the V3 loop in an extended conformation contains the amino acid sequence set forth as SEQ ID NO: 2. In other embodiments, the gp120 polypeptide with an extended v3 loop contains a portion of the amino acid sequence set forth as SED ID NO: 2, for example, a domain such as the outer domain, or a contiguous stretch of about 5 or more amino acids, such as about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, or more amino acids wherein the domain or contiguous stretch of amino acids includes a portion of the V3 loop.

Other embodiments are compositions containing a therapeutically effective amount of at least one gp120 polypeptide, such as a stabilized gp120 polypeptide (such as set forth as SEQ ID NO: 1 or as encoded by the nucleotide sequence set forth as one of SEQ ID NO: 4, 5, 6, 7, 8, 10, 11, 12, 13, 14 15, 16, 17, and 18, or a degenerate variant thereof) or a gp120 polypeptide with the V3 loop in an extended conformation, such as the amino acid sequence set forth as SEQ NO: 2. In some embodiments, the composition can contain pharmaceutically acceptable carriers, adjuvants, or combinations thereof.

This disclosure further provides methods for eliciting and/or enhancing an immune response in a subject (such as a primate subject, for example a human subject). In some embodiments, these methods involve administering to the subject a composition including a gp120 polypeptide as disclosed herein, for example a stabilized gp120 such as set forth as SEQ ID NO: 1 or as encoded by the nucleotide sequence set forth as one of SEQ ID NO: 4, 5, 6, 7, 8, 10, 11, 12, 13, 14 15, 16, 17, and 18, or a degenerate variant thereof. In some embodiments, these methods involve administering to the subject a composition including a gp120 polypeptide with an extended V3 loop such as set forth as SEQ ID NO: 2. In one specific, non-limiting example, the subject is infected with a lentivirus, for example SIV or HIV, such as HIV-1 or HIV-2. In some embodiments, the immune response is a B cell response, a T cell response, or a combination thereof.

In other embodiments, the subject is further administered a therapeutically effective amount of a monomeric or trimeric gp140 polypeptide, an unmodified monomeric or trimeric gp120 polypeptide, or a combination thereof.

Other embodiments of this disclosure are isolated polynucleotides (nucleic acid molecules) which encode the gp120 polypeptides described herein. Specific examples of such nucleic acid molecules contain nucleic acids encoding the amino acid sequence set forth as one of SEQ ID NO: 1 or 2, the nucleotide sequences set forth as one of SEQ ID NOs: 4-18, or degenerate variants thereof. In other embodiments, the isolated polynucleotides consist of nucleic acid molecules encoding the amino acid sequence set forth as one of SEQ ID NO: 1 or 2, the nucleotide sequences set forth as one of SEQ ID NOs: 4-18, or degenerate variants thereof. In certain embodiments, the nucleic acid encoding a gp120 polypeptide is operably linked to a promoter. Vectors comprising such polynucleotides are also disclosed, as are host cells transformed with such vectors.

Other embodiments are compositions containing a therapeutically effective amount of a polynucleotide containing a nucleic acid encoding a gp120 polypeptide disclosed herein. In certain embodiments, the nucleic acid encodes the amino acid sequence set forth as SEQ ID NO: 1 and 2. In other embodiments the nucleic acid contains the one of the nucleotide sequences set forth as SEQ ID NO: 4-18 or a degenerate variant thereof. In some embodiments, the composition can contain pharmaceutically acceptable carriers, adjuvants, or combinations thereof.

This disclosure further provides methods for eliciting and/or enhancing an immune response in a subject (such as a primate subject, for example a human subject). The methods involve administering to the subject a composition containing a nucleic acid encoding a gp120 polypeptide of this disclosure. In one specific, non-limiting example, the subject is infected with a lentivirus, for example SIV or HIV, such as HIV-1 or HIV-2. In some embodiments, the immune response is a B cell response, a T cell response, or a combination thereof.

In other embodiments, the subject is further administered a therapeutically effective amount of a plasmid vector expressing a polypeptide containing a monomeric or trimeric gp140 polypeptide, an unmodified monomeric or trimeric gp120 polypeptide; or combination thereof.

Also disclosed herein are methods for identifying an immunogen that induces an immune response to gp120, for example gp120 from a lentivirus, such as SIV or HIV such as HIV-1 or HIV-2. Typically the immune response is a B cell response, a T cell response, or a combination thereof. These methods involve using a three-dimensional structure of gp120 as defined by atomic coordinates set forth in Table 1, Table 2, or a portion thereof to design or select the immunogen, synthesizing the immunogen, immunizing a subject with the immunogen; and determining if an immune response to gp120 is induced in the subject. In some embodiments, the immunogen is designed from the gp120 amino acid sequence. In certain embodiments, the immunogen is designed or selected using a three-dimensional structure of gp120 as defined by atomic coordinates set forth in Table 1, Table 2, or a portion thereof and an amino acid sequence is assembled to provide an immunogen, for example by synthesizing the amino acid sequence or producing a nucleic acid encoding the immunogen. In other embodiments the is selected from a database of compounds or is designed de novo.

Also provided by this disclosure is a machine readable data storage medium including a data storage material encoded with machine readable data corresponding to the coordinates of a stabilized form of gp120 as defined by Table 1 or a portion thereof or a form of gp120 having an extended conformation of the V3 loop as defined by Table 2 or a portion thereof.

Also provided for are computer systems including data and a data processor, wherein the system forms a representation of the three-dimensional structure gp120 protein as defined by Table 1, Table 2, or a portion thereof, such as the atomic positions, surface, domain, or region of the gp120 polypeptide.

Also disclosed herein is the use of stabilized gp120 molecules as crystallization tools. A crystalline form of a stabilized gp120 also is disclosed, for example the crystalline form of gp120 as defined by the coordinates as given in Table 1, or with coordinates having a root mean square deviation therefrom, wherein the distance between the residues is less than about 0.75 Å. A crystalline form of a gp120 with an extended V3 loop also is disclosed, for example the crystalline form of gp120 as defined by the coordinates as given in Table 2, or with coordinates having a root mean square deviation therefrom, wherein the distance between the residues is less than about 0.75 Å.

III. gp120 Immunogens and Nucleic Acids Encoding gp120 Immunogens

The present disclosure relates to gp120 polypeptides and nucleic acids encoding these gp120 polypeptides. The gp120 polypeptides of this disclosure are capable of eliciting an immune response to a gp120 protein in a subject, such as a human subject. In some embodiments, the gp120 polypeptides of this disclosure are stabilized in a CD4 bound conformation.

Using a combination of atomic level structural information with biophysical techniques novel gp120 polypeptides were designed that are stabilized in the conformation substantially identical to the CD4 bound polypeptide. For example, the three-dimensional structure of the wild-type polypeptide was analyzed to determine where cysteine residues could be introduced such that they would form disulfide bonds in the folded molecule. This methodology is not specific to cysteine residues; other natural or non-natural amino acids could be used. In some embodiments, the stabilized gp120 has a K_(d) for CD4 of less than or equal to about 10 nM, such as less than or equal to about 5 nM, less than or equal to about 3 nM, or less than or equal to about 1 nM. In some embodiments the stabilized gp120 has −TΔS for CD4 binding of about less than or equal to 40 kcal/mol, such as about less than or equal to 30 kcal/mol, about less than or equal to 15 kcal/mol, or about less than or equal to 10 kcal/mol.

The stability of folded polypeptides can be measured using techniques such as thermal denaturation. The temperature of the unfolding transition (T_(m)) is an accepted measure of the stability of the folded polypeptide, where increases in T_(m) indicate an increase in the stability of the folded polypeptide. In some embodiments, the stabilized gp120 polypeptides has a T_(m) value greater than about 52° C., such as greater than about 53° C., greater than about 54° C. (such as 53.8° C.), greater than about 55° C., greater than about 56° C., greater than about 57° C., greater than about 58° C., or even greater than about 59° C.

In some embodiments, the stabilized gp120 polypeptides are stabilized by a plurality of non-naturally occurring cross-linking cysteine residues. By plurality it is meant that there are at least 2, such as at least 4, at least 6, or at least 8 cysteines introduced by mutation into a gp120 polypeptide, such that pairs of cysteines form at least 1, such as at least 2, at least 3, or at least 4 disulfide bonds. Each disulfide bond is formed by a pair of cysteines.

In some embodiments, the mutationally introduced cysteines are introduced into the gp120 polypeptide at positions 96, 109, 123, 231, 267, 275, 428, 431, or in a sub-combination thereof. In some examples of the stabilized gp120 polypeptides, the plurality of non-naturally occurring cross-linking cysteine residues are defined by the interaction of at least one of residue pairs 96 and 275; 109 and 428; 123 and 431; and 231 and 267. Thus, the stabilized gp120 polypeptides of this disclosure may have any combination of the crosslinked cysteines defined by the interaction of 96 and 275; 109 and 428; 123 and 431; and 231 and 267.

In some embodiments, the stabilized gp120 polypeptide contains one or more amino acid substitutions in the protein core. In several disclosed examples, the substitution is made at position 95, 257, 375, 433, or a combination thereof. Thus, a stabilized gp120 polypeptide may have one, two, three, or four substitutions in the protein core. In specific examples, the substitution is a serine to tryptophan substitution at position 95, a threonine to serine substitution at position 257, a serine to tryptophan substitution at position 375, an alanine to methionine substitution at position 433, or various combinations thereof.

In one embodiment, the stabilized gp120 polypeptide (new_(—)9c) includes the amino acid sequence set forth as:

(SEQ ID NO: 1) EVVLVNVTENFNWCKNDMVEQMHEDICSLWDQSLKPCVKLCPLAGATSVI TQACPKVSFEPIPIHYCAPAGFAILKCNNKTFNGTGPCTNVSTVQCTHGI RPVVSSQLLLNGSLAEEEVVIRSCNFTDNAKTIIVQLNTSVEINCTRPNN GGSGSGGNMRQAHCNISRAKWNNTLKQIASKLREQFGNNKTIIFKQSSGG DPEIVTHWFNCGGEFFYCNSTQLFNSTWFNSTWSTEGSNNTEGSDTITLP CRIKQIINMWCKVCKAMYAPPISGQIRCSSNITGLLLTRDGGNSNNESEI FRPGGGDMRDNWRSELYKYKVVKIE.

In other embodiments, the stabilized gp120 includes the amino acid sequence encoded by one of SEQ ID NO: 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 16, 17, and 18, or degenerate variants thereof. In still other embodiments, the stabilized gp120 polypeptide consists of the amino acid sequence set forth as SEQ ID NO: 1 or as encoded by the nucleotide sequence set forth as one of SEQ ID NO: 4, 5, 6, 7, 8, 10, 11, 12, 13, 14 15, 16, 17, and 18, or a degenerate variant thereof. In some embodiments, a stabilized gp120 polypeptide is an immunogenic fragment of SEQ ID NO: 1 or as encoded by the nucleotide sequence set forth as one of SEQ ID NO: 4, 5, 6, 7, 8, 10, 11, 12, 13, 14 15, 16, 17, and 18, or a degenerate variant thereof, such that the immunogenic fragment is stabilized in a CD4 binding conformation. In some embodiments, the stabilized gp120 includes the outer-domain. In one example, the outer domain includes residues 255-421 and 436-474 of gp120. Thus, the outer domain can contain residues 109-246 and 261-299 of SEQ ID NO: 1, the amino acid sequence encoded by SEQ ID NO: 4-18 or a degenerate variant thereof. In some examples residues 246 and 261 are covalently linked, for example by a peptide linker. In some examples, the peptide linker is residues 247-260 of SEQ ID NO: 1, the amino acid sequence encoded by SEQ ID NO: 4-18 or a degenerate variant thereof. Ideally the linker should be of sufficient length such that the folded protein is a conformation that can be bound by CD4. In some embodiments, the linker is a peptide linker and the peptide linker is about 2 to about 20 amino acids in length, such as about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 10, about 12, about 15, or about 20 amino acids in length. In some embodiments, the immunogenic fragment of gp120 consists of residues 109-246 and 261-299, and a linker. In some embodiments the linker does not contain a sequence form gp120.

In other embodiments, the stabilized gp120 fragment is truncated on the carboxy terminal end. For example, the carboxy terminal end can be truncated to about amino acid residue 433. In addition, portions of the amino terminus of gp120 can also be eliminated from the stabilized gp120 fragment. The truncated gp120 sequence can be free from the carboxy terminus through amino acid residue 95. In one embodiment, the truncated gp120 sequence is free from the amino terminus of gp120 through residue 95 and residue 433 through the carboxy terminus of gp120. Thus, in some embodiments the stabilized gp120 contains a portion of the amino acid sequence set forth as SEQ ID NO: 1 or as encoded by any one of SED NOs:4-18.

In other embodiments, the gp120 polypeptide has the V3 loop in an extended conformation. An exemplary sequence of a gp120 with an extended loop is set forth as:

(SEQ ID NO: 2) GARSEVVLENVTEHFNMWKNDMVEQMQEDIISLWDQSLKPCVKLTPLCVG AGSCDTSVITQACPKISFEPIPIHYCAPAGFAILKCNDKTFNGKGPCKNV STVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSDNFTNNAKTIIVQLKESV EINCTRPNQNTRKSIHIGPGRAFYTTGEIIGDIRQAHCNISRAKWNDTLK QIVIKLREQFENKTIVFNHSSGGDPEIVMHSFNCGGEFFYCNSAQLFNST WNNNTEGSNNTEGNTITLPCRIKQIINMWQEVGKAMYAPPIRGQIRCSSN ITGLLLTRDGGINENGTEIFRPGGGDMRDNWRSELYKYKVVKIE.

Thus, a gp120 polypeptide with an extended V3 loop can contain the amino acid sequence set forth as SEQ ID NO: 2 or a fragment thereof. In one example, the gp120 polypeptide with the V3 loop in an extended conformation consists of the amino acid sequence set forth as SEQ ID NO: 2 or a fragment thereof. In still other embodiments, the gp120 polypeptide with an extended V3 loop contains a portion of the amino acid sequence set forth as SED ID NO: 2. In some embodiments, the stabilized gp120 includes the outer-domain. In one example, the outer domain includes residues 255-421 and 436-474 of gp120. Thus, the outer domain can include residues 109-246 and 261-299 of SEQ ID NO: 2.

In other embodiments, the gp120 polypeptide has the V3 loop in an extended conformation is truncated on the carboxy terminal end. For example, the carboxy terminal end can be truncated to about amino acid residue 433. In addition, portions of the amino terminus of gp120 can also be eliminated from the gp120 polypeptide has the V3 loop in an extended conformation fragment. The truncated gp120 sequence can be free from the carboxy terminus through amino acid residue 95. In one embodiment, the truncated gp120 sequence is free from the amino terminus of gp120 through residue 95 and residue 433 through the carboxy terminus of gp120. Thus, in some embodiments the gp120 polypeptide has the V3 loop in an extended conformation contains a portion of the amino acid sequence set forth as SEQ ID NO: 2.

In other embodiments, the gp120 polypeptide has an amino acid sequence least 90% identical to SEQ ID NO: 1, SEQ ID NO: 2, or the amino acid sequence encoded by any one of SEQ ID NO: 4-18, for example a polypeptide that has about 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or even higher sequence identity to SEQ ID NO: 1, SEQ ID NO: 2, or the amino acid sequence encoded by any one of SEQ ID NO: 4-18.

The immunogenic gp120 polypeptides or immunogenic fragments of the gp120 polypeptides disclosed herein can be chemically synthesized by standard methods, or can be produced recombinantly. An exemplary process for polypeptide production is described in Lu et al., Federation of European Biochemical Societies Letters. 429:31-35, 1998. They can also be isolated by methods including preparative chromatography and immunological separations.

In other embodiments, fusion proteins are provided including a first and second polypeptide moiety in which one of the protein moieties includes an amino acid sequence as set forth in SEQ ID NO: 1 or 2, or a fragment thereof. In other embodiments, fusion proteins are provided comprising a first and second polypeptide moiety in which one of the protein moieties includes an amino acid sequence encoded by one of the nucleotide sequences as set forth as SEQ ID NO: 4-18, or a fragment thereof. The other moiety is a heterologous protein such as can be a carrier protein and/or an immunogenic protein. Such fusions also are useful to evoke an immune response against gp120. In certain embodiments the gp120 polypeptides disclosed herein are co-valent or non-covalent addition of TLR ligands or dendritic cell or B cell targeting moieties.

A gp120 polypeptide can be covalently linked to a carrier, which is an immunogenic macromolecule to which an antigenic molecule can be bound. When bound to a carrier, the bound polypeptide becomes more immunogenic. Carriers are chosen to increase the immunogenicity of the bound molecule and/or to elicit higher titers of antibodies against the carrier which are diagnostically, analytically, and/or therapeutically beneficial. Covalent linking of a molecule to a carrier can confer enhanced immunogenicity and T cell dependence (see Pozsgay et al., PNAS 96:5194-97, 1999; Lee et al., J. Immunol. 116:1711-18, 1976; Dintzis et al., PNAS 73:3671-75, 1976). Useful carriers include polymeric carriers, which can be natural (for example, polysaccharides, polypeptides or proteins from bacteria or viruses), semi-synthetic or synthetic materials containing one or more functional groups to which a reactant moiety can be attached. Bacterial products and viral proteins (such as hepatitis B surface antigen and core antigen) can also be used as carriers, as well as proteins from higher organisms such as keyhole limpet hemocyanin, horseshoe crab hemocyanin, edestin, mammalian serum albumins, and mammalian immunoglobulins. Additional bacterial products for use as carriers include bacterial wall proteins and other products (for example, streptococcal or staphylococcal cell walls and lipopolysaccharide (LPS)).

Most antigenic epitopes of HIV proteins are relatively small in size, such as about 5 to 100 amino acids in size, for example about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 40, about 50, about 60, about 70, about 80, about 90, or about 100. Thus, fragments (for example, epitopes or other antigenic fragments) of a gp120 polypeptide, such as any of the gp120 polypeptides described herein or a fragment thereof, can be used as an immunogen.

In some embodiments, the disclosed gp120 polypeptides are modified by glycosylation, for example by N-linked glycans. Thus, the immune response can be focused on a region interest of a gp120 polypeptide by masking other regions with non-immunogenic glycans. Glycosylation sites can be introduced into the gp120 polypeptides by site directed mutagenesis. This straggly can be utilized to focus the immune response to regions of interest in the gp120 polypeptide, for example the CD4 binding site or the binding site for a neutralizing antibody, for example a the b12 antibody. Examples of glycan masking can be found in Pantophlet and Burton, Trends Mol Med. 9(11):468-73, 2003, which is incorporated by reference herein in its entirety.

Another strategy to focus the immune response on the CD4 binding region or b12 epitope region is to use SIV and HIVgp120 core glycoproteins (such as the stabilized gp120 polypeptides disclosed herein) that possess an endogenous CD4 binding site or to scaffold the heterologous HIV-1 CD4 binding region onto cores derived from selected SIV or HIV-2 strains. The gp120 core can be derived from the envelope glycoproteins of letivius, for example SIV such as SIV mac239 and HIV, such as HIV-2 7132A. The residues required for CD4BS antibody recognition, for example the site of b12 binding, are transplanted by site-directed mutagenesis of the appropriate codon-optimized plasmid sequences. In some embodiments, extra N-glycans are added to these cores to eliminate the elicitation of non-cross reactive antibodies directed against regions outside the antibody binding site, for example the binding site of a neutralizing antibody such as CD4BS antibody.

The present disclosure concerns nucleic acid constructs including polynucleotide sequences that encode antigenic gp120 polypeptides of HIV-1. These polynucleotides include DNA, cDNA and RNA sequences which encode the polypeptide of interest.

Methods for the manipulation and insertion of the nucleic acids of this disclosure into vectors are well known in the (see for example, Sambrook et al., Molecular Cloning, a Laboratory Manual, 2d edition, Cold Spring Harbor Press, Cold Spring Harbor, N.Y., 1989, and Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates and John Wiley & Sons, New York, N.Y., 1994).

Typically, the nucleic acid constructs encoding the gp120 polypeptides of this disclosure are plasmids. However, other vectors (for example, viral vectors, phage, cosmids, etc.) can be utilized to replicate the nucleic acids. In the context of this disclosure, the nucleic acid constructs typically are expression vectors that contain a promoter sequence which facilitates the efficient transcription of the inserted genetic sequence of the host. The expression vector typically contains an origin of replication, a promoter, as well as specific nucleic acid sequences that allow phenotypic selection of the transformed cells.

More generally, polynucleotide sequences encoding the gp120 polypeptides of this disclosure can be operably linked to any promoter and/or enhancer that is capable of driving expression of the nucleic acid following introduction into a host cell. A promoter is an array of nucleic acid control sequences that directs transcription of a nucleic acid. A promoter includes necessary nucleic acid sequences (which can be) near the start site of transcription, such as in the case of a polymerase II type promoter (a TATA element). A promoter also can include distal enhancer or repressor elements which can be located as much as several thousand base pairs from the start site of transcription. Both constitutive and inducible promoters are included (see, for example, Bitter et al., Methods in Enzymology 153:516-544, 1987).

To produce such nucleic acid constructs, polynucleotide sequences encoding gp120 polypeptides are inserted into a suitable expression vector, such as a plasmid expression vector. Procedures for producing polynucleotide sequences encoding gp120 polypeptides and for manipulating them in vitro are well known to those of skill in the art, and can be found, for example in Sambrook and Ausubel, supra.

In addition to the polynucleotide sequences encoding the polypeptides set forth as SEQ ID NOs:1-2 disclosed herein and nucleic acids encoding gp120 polypeptides as set forth as SEQ ID NOs:4-18 as disclosed herein, the nucleic acid constructs can include variant polynucleotide sequences that encode polypeptides that are substantially similar to SEQ ID NOs: 1-2 and nucleic acids encoding gp120 polypeptides as set forth as SEQ ID NOs: 4-18. Similarly, the nucleic acid constructs can include polynucleotides that encode chimeric polypeptides, for example fusion proteins. For enhanced immunogenicity, it may be advantageous to include the sequence encoding for heterologous T helper sequences derived from HIV or other heterologous sources.

The similarity between amino acid (and polynucleotide) sequences is expressed in terms of the similarity between the sequences, otherwise referred to as sequence identity. Sequence identity is frequently measured in terms of percentage identity (or similarity); the higher the percentage, the more similar are the primary structures of the two sequences. In general, the more similar the primary structures of two amino acid sequences, the more similar are the higher order structures resulting from folding and assembly. Thus, the nucleic acid constructs can include polynucleotides that encode polypeptides that are at least about 90%, or 95%, 98%, or 99% identical to one of SEQ ID NOs: 1-2 with respect to amino acid sequence, or that have at least about 90%, 95%, 98%, or 99% sequence identity to one or more of SEQ ID NOs: 4-18 and/or that differ from one of these sequences by the substitution of degenerate codons.

DNA sequences encoding an immunogenic gp120 polypeptide can be expressed in vitro by DNA transfer into a suitable host cell. The cell may be prokaryotic or eukaryotic. The term also includes any progeny of the subject host cell. It is understood that all progeny may not be identical to the parental cell since there may be mutations that occur during replication. Methods of stable transfer, meaning that the foreign DNA is continuously maintained in the host, are known in the art.

The polynucleotide sequences encoding an immunogenic gp120 polypeptide can be inserted into an expression vector including, but not limited to, a plasmid, virus or other vehicle that can be manipulated to allow insertion or incorporation of sequences and can be expressed in either prokaryotes or eukaryotes. Hosts can include microbial, yeast, insect, and mammalian organisms. Methods of expressing DNA sequences having eukaryotic or viral sequences in prokaryotes are well known in the art. Biologically functional viral and plasmid DNA vectors capable of expression and replication in a host are known in the art.

Transformation of a host cell with recombinant DNA can be carried out by conventional techniques that are well known to those of ordinary skill in the art. Where the host is prokaryotic, such as E. coli, competent cells which are capable of DNA uptake can be prepared from cells harvested after exponential growth phase and subsequently treated by the CaCl₂ method using procedures well known in the art. Alternatively, MgCl₂ or RbCl can be used. Transformation can also be performed after forming a protoplast of the host cell if desired, or by electroporation.

When the host is a eukaryote, such methods of transfection of DNA as calcium phosphate coprecipitates, conventional mechanical procedures such as microinjection, electroporation, insertion of a plasmid encased in liposomes, or virus vectors can be used. Eukaryotic cells can also be co-transformed with polynucleotide sequences encoding an immunogenic gp120 polypeptide, and a second foreign DNA molecule encoding a selectable phenotype, such as the herpes simplex thymidine kinase gene. Another method is to use a eukaryotic viral vector, such as simian virus 40 (SV40) or bovine papilloma virus, to transiently infect or transform eukaryotic cells and express the protein (see for example, Eukaiyotic Viral Vectors, Cold Spring Harbor Laboratory, Gluzman ed., 1982).

IV. Immunogenic Compositions and Therapeutic Methods

Any of the gp120 polypeptides and nucleic acid molecules encoding the gp120 polypeptides disclosed herein can be used as immunogens, or to produce immunogens to elicit an immune response (immunogenic compositions) to gp120 such as to a gp120 expressing virus, for example to reduce HIV-1 infection or a symptom of HIV-1 infection. Following administration of a therapeutically effective amount of the disclosed therapeutic compositions, the subject can be monitored for HIV-1 infection, symptoms associated with HIV-1 infection, or both. Disclosed hereinare methods of administering the therapeutic molecules disclosed herein (such as gp120 polypeptides and nucleic acids encoding gp120 polypeptides) to reduce HIV-1 infection. In several examples, a therapeutically effective amount of a gp120 polypeptide including SEQ ID NO: 1, a therapeutically effective amount of a gp120 polypeptide including SEQ ID NO: 2, a therapeutically effective amount of a gp120 polypeptide encoded by one of SEQ ID NOs: 4-18 or a degenerate variant thereof, or a combination thereof is administered to a subject.

In certain embodiments, the immunogenic composition includes an adjuvant. An adjuvant can be a suspension of minerals, such as alum, aluminum hydroxide, aluminum phosphate, on which antigen is adsorbed; or water-in-oil emulsion in which antigen solution is emulsified in oil (MF-59, Freund's incomplete adjuvant), sometimes with the inclusion of killed mycobacteria (Freund's complete adjuvant) to further enhance antigenicity (inhibits degradation of antigen and/or causes influx of macrophages). In one embodiment, the adjuvant is a mixture of stabilizing detergents, micelle-forming agent, and oil available under the name PROVAX® (IDEC Pharmaceuticals, San Diego, Calif.). An adjuvant can also be an immunostimulatory nucleic acid, such as a nucleic acid including a CpG motif.

In one example, the immunogenic composition is mixed with an adjuvant containing two or more of a stabilizing detergent, a micelle-forming agent, and an oil. Suitable stabilizing detergents, micelle-forming agents, and oils are detailed in U.S. Pat. Nos. 5,585,103; 5,709,860; 5,270,202; and 5,695,770, all of which are incorporated by reference herein in their entirety. A stabilizing detergent is any detergent that allows the components of the emulsion to remain as a stable emulsion. Such detergents include polysorbate 80 (TWEEN) (Sorbitan-mono-9-octadecenoate-poly(oxy-1,2-ethanediyl; manufactured by ICI Americas, Wilmington, Del.), TWEEN 40™, TWEEN 20™, TWEEN60™, ZWITTERGENT™ 3-12, TEEPOL HB7™, and SPAN85™. These detergents are usually provided in an amount of approximately 0.05 to 0.5%, such as at about 0.2%. A micelle forming agent is an agent which is able to stabilize the emulsion formed with the other components such that a micelle-like structure is formed. Such agents generally cause some irritation at the site of injection in order to recruit macrophages to enhance the cellular response. Examples of such agents include polymer surfactants described by BASF Wyandotte publications, for example, Schmolka, J. Am. Oil. Chem. Soc. 54:110, 1977, and Hunter et al., J. Immunol 129:1244, 1981, PLURONIC™ L62LF, L101, and L64, PEG1000, and TETRONIC™ 1501, 150R1, 701, 901, 1301, and 130R1. The chemical structures of such agents are well known in the art. In one embodiment, the agent is chosen to have a hydrophile-lipophile balance (HLB) of between 0 and 2, as defined by Hunter and Bennett, J. Immun. 133:3167, 1984. The agent can be provided in an effective amount, for example between 0.5 and 10%, or in an amount between 1.25 and 5%.

The oil included in the composition is chosen to promote the retention of the antigen in oil-in-water emulsion, to provide a vehicle for the desired antigen, and preferably has a melting temperature of less than 65° C. such that emulsion is formed either at room temperature (about 20° C. to 25° C.), or once the temperature of the emulsion is brought down to room temperature. Examples of such oils include squalene, Squalane, EICOSANE™, tetratetracontane, glycerol, and peanut oil or other vegetable oils. In one specific, non-limiting example, the oil is provided in an amount between 1 and 10%, or between 2.5 and 5%. The oil should be both biodegradable and biocompatible so that the body can break down the oil over time, and so that no adverse affects, such as granulomas, are evident upon use of the oil.

Immunogenic compositions can be formulated with an appropriate solid or liquid carrier, depending upon the particular mode of administration chosen. If desired, the disclosed pharmaceutical compositions can also contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate. Excipients that can be included in the disclosed compositions include flow conditioners and lubricants, for example silicic acid, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol, or derivatives thereof.

Immunogenic compositions can be provided as parenteral compositions, such as for injection or infusion. Such compositions are formulated generally by mixing a disclosed therapeutic agent at the desired degree of purity, in a unit dosage injectable form (solution, suspension, or emulsion), with a pharmaceutically acceptable carrier, for example one that is non-toxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation. In addition, a disclosed therapeutic agent can be suspended in an aqueous carrier, for example, in an isotonic buffer solution at a pH of about 3.0 to about 8.0, preferably at a pH of about 3.5 to about 7.4, 3.5 to 6.0, or 3.5 to about 5.0. Useful buffers include sodium citrate-citric acid and sodium phosphate-phosphoric acid, and sodium acetate/acetic acid buffers. The active ingredient, optionally together with excipients, can also be in the form of a lyophilisate and can be made into a solution prior to parenteral administration by the addition of suitable solvents. Solutions such as those that are used, for example, for parenteral administration can also be used as infusion solutions.

A form of repository or “depot” slow release preparation can be used so that therapeutically effective amounts of the preparation are delivered into the bloodstream over many hours or days following transdermal injection or delivery. Such long acting formulations can be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. The compounds can be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.

Immunogenic compositions that include a disclosed therapeutic agent can be delivered by way of a pump (see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng. 14:201, 1987; Buchwald et al., Surgery 88:507, 1980; Saudek et al., N. Engl. J. Med. 321:574, 1989) or by continuous subcutaneous infusions, for example, using a mini-pump. An intravenous bag solution can also be employed. One factor in selecting an appropriate dose is the result obtained, as measured by the methods disclosed here, as are deemed appropriate by the practitioner. Other controlled release systems are discussed in Langer (Science 249:1527-33, 1990).

In one example, a pump is implanted (for example see U.S. Pat. Nos. 6,436,091; 5,939,380; and 5,993,414). Implantable drug infusion devices are used to provide patients with a constant and long-term dosage or infusion of a therapeutic agent. Such device can be categorized as either active or passive.

Active drug or programmable infusion devices feature a pump or a metering system to deliver the agent into the patient's system. An example of such an active infusion device currently available is the Medtronic SYNCHROMED™ programmable pump. Passive infusion devices, in contrast, do not feature a pump, but rather rely upon a pressurized drug reservoir to deliver the agent of interest. An example of such a device includes the Medtronic ISOMED™.

In particular examples, immunogenic compositions including a disclosed therapeutic agent are administered by sustained-release systems. Suitable examples of sustained-release systems include suitable polymeric materials (such as, semi-permeable polymer matrices in the form of shaped articles, for example films, or microcapsules), suitable hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, and sparingly soluble derivatives (such as, for example, a sparingly soluble salt). Sustained-release compositions can be administered orally, parenterally, intracistemally, intraperitoneally, topically (as by powders, ointments, gels, drops or transdermal patch), or as an oral or nasal spray. Sustained-release matrices include polylactides (U.S. Pat. No. 3,773,919, EP 58,481), copolymers of L-glutamic acid and gamma-ethyl-L-glutamate (Sidman et al., Biopolymers 22:547-556, 1983, poly(2-hydroxyethyl methacrylate)); (Langer et al., J. Biomed. Mater. Res. 15:167-277, 1981; Langer, Chem. Tech. 12:98-105, 1982, ethylene vinyl acetate (Langer et al., Id.) or poly-D-(−)-3-hydroxybutyric acid (EP 133,988).

Polymers can be used for ion-controlled release. Various degradable and nondegradable polymeric matrices for use in controlled drug delivery are known in the art (Langer, Accounts Chem. Res. 26:537, 1993). For example, the block copolymer, polaxamer 407 exists as a viscous yet mobile liquid at low temperatures but forms a semisolid gel at body temperature. It has shown to be an effective vehicle for formulation and sustained delivery of recombinant interleukin-2 and urease (Johnston et al., Pharm. Res. 9:425, 1992; and Pec, J. Parent. Sci. Tech. 44(2):58, 1990). Alternatively, hydroxyapatite has been used as a microcarrier for controlled release of proteins (Ijntema et al., Int. J. Pharm. 112:215, 1994). In yet another aspect, liposomes are used for controlled release as well as drug targeting of the lipid-capsulated drug (Betageri et al., Liposome Drug Delivery Systems, Technomic Publishing Co., Inc., Lancaster, Pa., 1993). Numerous additional systems for controlled delivery of therapeutic proteins are known (for example, U.S. Pat. Nos. 5,055,303; 5,188,837; 4,235,871; 4,501,728;. 4,837,028; 4,957,735; and 5,019,369; 5,055,303; 5,514,670; 5,413,797; 5,268,164; 5,004,697; 4,902,505; 5,506,206; 5,271,961; 5,254,342; and 5,534,496).

Immunogenic compositions can be administered for therapeutic treatments. In therapeutic applications, a therapeutically effective amount of the immunogenic composition is administered to a subject suffering from a disease, such as HIV-1 infection or AIDS. The immunogenic composition an be administered by any means known to one of skill in the art (see Banga, A., “Parenteral Controlled Delivery of Therapeutic Peptides and Proteins,” in Therapeutic Peptides and Proteins, Technomic Publishing Co., Inc., Lancaster, Pa., 1995) such as by intramuscular, subcutaneous, or intravenous injection, but even oral, nasal, or anal administration is contemplated. To extend the time during which the peptide or protein is available to stimulate a response, the peptide or protein can be provided as an implant, an oily injection, or as a particulate system. The particulate system can be a microparticle, a microcapsule, a microsphere, a nanocapsule, or similar particle (see, for example, Banga, supra). A particulate carrier based on a synthetic polymer has been shown to act as an adjuvant to enhance the immune response, in addition to providing a controlled release. Aluminum salts can also be used as adjuvants to produce an immune response.

Immunogenic compositions can be formulated in unit dosage form, suitable for individual administration of precise dosages. In pulse doses, a bolus administration of an immunogenic composition that includes a disclosed immunogen is provided, followed by a time-period wherein no disclosed immunogen is administered to the subject, followed by a second bolus administration. A therapeutically effective amount of an immunogenic composition can be administered in a single dose, or in multiple doses, for example daily, during a course of treatment. In specific, non-limiting examples, pulse doses of an immunogenic composition that include a disclosed immunogen are administered during the course of a day, during the course of a week, or during the course of a month.

Immunogenic compositions can be administered whenever the effect (such as decreased signs, symptom, or laboratory results of HIV-1 infection) is desired. Generally, the dose is sufficient to treat or ameliorate symptoms or signs of disease without producing unacceptable toxicity to the subject. Systemic or local administration can be utilized.

Amounts effective for therapeutic use can depend on the severity of the disease and the age, weight, general state of the patient, and other clinical factors. Thus, the final determination of the appropriate treatment regimen will be made by the attending clinician. Typically, dosages used in vitro can provide useful guidance in the amounts useful for in situ administration of the pharmaceutical composition, and animal models may be used to determine effective dosages for treatment of particular disorders. Various considerations are described, for example in Gilman et al., eds., Goodman and Gilman: The Pharmacological Bases of Therapeutics, 8th ed., Pergamon Press, 1990; and Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Co., Easton, Pa., 1990. Typically, the dose range for a gp120 polypeptide is from about 0.1 μg/kg body weight to about 100 mg/kg body weight. Other suitable ranges include doses of from about 1 μg/kg to 10 mg/kg body weight. In one example, the dose is about 1.0 μg to about 50 mg, for example, 1 μg to 1 mg, such as 1 mg peptide per subject. The dosing schedule can vary from daily to as seldom as once a year, depending on clinical factors, such as the subject's sensitivity to the peptide and tempo of their disease. Therefore, a subject can receive a first dose of a disclosed therapeutic molecule, and then receive a second dose (or even more doses) at some later time(s), such as at least one day later, such as at least one week later.

The pharmaceutical compositions disclosed herein can be prepared and administered in dose units. Solid dose units include tablets, capsules, transdermal delivery systems, and suppositories. The administration of a therapeutic amount can be carried out both by single administration in the form of an individual dose unit or else several smaller dose units and also by multiple administrations of subdivided doses at specific intervals. Suitable single or divided doses include, but are not limited to about 0.01, 0.1, 0.5, 1, 3, 5, 10, 15, 30, or 50 μg protein/kg/day

The nucleic acid constructs encoding antigenic gp120 polypeptides described herein are used, for example, in combination, as pharmaceutical compositions (medicaments) for use in therapeutic, for example, prophylactic regimens (such as vaccines) and administered to subjects (for example, primate subjects such as human subjects) to elicit an immune response against one or more clade or strain of HIV. For example, the compositions described herein can be administered to a human (or non-human) subject prior to infection with HIV to inhibit infection by or replication of the virus. Thus, the pharmaceutical compositions described above can be administered to a subject to elicit a protective immune response against HIV. To elicit an immune response, a therapeutically effective (for example, immunologically effective) amount of the nucleic acid constructs are administered to a subject, such as a human (or non-human) subject.

Immunization by nucleic acid constructs is well known in the art and taught, for example, in U.S. Pat. No. 5,643,578 (which describes methods of immunizing vertebrates by introducing DNA encoding a desired antigen to elicit a cell-mediated or a humoral response), and U.S. Pat. Nos. 5,593,972 and 5,817,637 (which describe operably linking a nucleic acid sequence encoding an antigen to regulatory sequences enabling expression). U.S. Pat. No. 5,880,103 describes several methods of delivery of nucleic acids encoding immunogenic peptides or other antigens to an organism. The methods include liposomal delivery of the nucleic acids (or of the synthetic peptides themselves), and immune-stimulating constructs, or ISCOMS™, negatively charged cage-like structures of 30-40 nm in size formed spontaneously on mixing cholesterol and QUIL A™ (saponin).

For administration of gp120 nucleic acid molecules, the nucleic acid can be delivered intracellularly, for example by expression from an appropriate nucleic acid expression vector which is administered so that it becomes intracellular, such as by use of a retroviral vector (see U.S. Pat. No. 4,980,286), or by direct injection, or by use of microparticle bombardment (such as a gene gun; Biolistic, Dupont), or coating with lipids or cell-surface receptors or transfecting agents, or by administering it in linkage to a homeobox-like peptide which is known to enter the nucleus (for example Joliot et al., Proc. Natl. Acad. Sci. USA 1991, 88:1864-8) The present disclosure includes all forms of nucleic acid delivery, including synthetic oligos, naked DNA, plasmid and viral, integrated into the genome or not.

In another approach to using nucleic acids for immunization, an immunogenic gp120 polypeptide can also be expressed by attenuated viral hosts or vectors or bacterial vectors. Recombinant vaccinia virus, adeno-associated virus (AAV), herpes virus, retrovirus, or other viral vectors can be used to express the peptide or protein, thereby eliciting a CTL response. For example, vaccinia vectors and methods useful in immunization protocols are described in U.S. Pat. No. 4,722,848. BCG (Bacillus Calmette Guerin) provides another vector for expression of the peptides (see Stover, Nature 351:456-460, 1991).

In one example, a viral vector is utilized. These vectors include, but are not limited to, adenovirus, herpes virus, vaccinia, or an RNA virus such as a retrovirus. In one example, the retroviral vector is a derivative of a murine or avian retrovirus. Examples of retroviral vectors in which a single foreign gene can be inserted include, but are not limited to: Moloney murine leukemia virus (MoMuLV), Harvey murine sarcoma virus (HaMuSV), murine mammary tumor virus (MuMTV), and Rous Sarcoma Virus (RSV). When the subject is a human, a vector such as the gibbon ape leukemia virus (GaLV) can be utilized. A number of additional retroviral vectors can incorporate multiple genes. All of these vectors can transfer or incorporate a gene for a selectable marker so that transduced cells can be identified and generated. By inserting a nucleic acid sequence encoding a gp120 polypeptide into the viral vector, along with another gene that encodes the ligand for a receptor on a specific target cell, for example, the vector is now target specific. Retroviral vectors can be made target specific by attaching, for example, a sugar, a glycolipid, or a protein. Preferred targeting is accomplished by using an antibody to target the retroviral vector. Those of skill in the art will know of, or can readily ascertain without undue experimentation, specific polynucleotide sequences which can be inserted into the retroviral genome or attached to a viral envelope to allow target specific delivery of the retroviral vector containing the polynucleotide encoding a gp120 polypeptide.

Since recombinant retroviruses are defective, they need assistance in order to produce infectious vector particles. This assistance can be provided, for example, by using helper cell lines that contain plasmids encoding all of the structural genes of the retrovirus under the control of regulatory sequences within the LTR. These plasmids are missing a nucleotide sequence that enables the packaging mechanism to recognize an RNA transcript for encapsidation. Helper cell lines that have deletions of the packaging signal include, but are not limited to Q2, PA317, and PA12, for example. These cell lines produce empty virions, since no genome is packaged. If a retroviral vector is introduced into such cells in which the packaging signal is intact, but the structural genes are replaced by other genes of interest, the vector can be packaged and vector virion produced.

Suitable formulations for the nucleic acid constructs, include aqueous and non-aqueous solutions, isotonic sterile solutions, which can contain anti-oxidants, buffers, and bacteriostats, and aqueous and non-aqueous sterile suspensions that can include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives. The formulations can be presented in unit-dose or multi-dose sealed containers, such as ampules and vials, and can be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example, water, immediately prior to use. Extemporaneous solutions and suspensions can be prepared from sterile powders, granules, and tablets. Preferably, the carrier is a buffered saline solution. More preferably, the composition for use in the inventive method is formulated to protect the nucleic acid constructs from damage prior to administration. For example, the composition can be formulated to reduce loss of the adenoviral vectors on devices used to prepare, store, or administer the expression vector, such as glassware, syringes, or needles. The compositions can be formulated to decrease the light sensitivity and/or temperature sensitivity of the components. To this end, the composition preferably comprises a pharmaceutically acceptable liquid carrier, such as, for example, those described above, and a stabilizing agent selected from the group consisting of polysorbate 80, L-arginine, polyvinylpyrrolidone, trehalose, and combinations thereof.

In therapeutic applications, a therapeutically effective amount of the composition is administered to a subject prior to or following exposure to or infection by HIV. When administered prior to exposure, the therapeutic application can be referred to as a prophylactic administration (such as in the form of a vaccine). Single or multiple administrations of the compositions are administered depending on the dosage and frequency as required and tolerated by the subject. In one embodiment, the dosage is administered once as a bolus, but in another embodiment can be applied periodically until a therapeutic result, such as a protective immune response, is achieved. Generally, the dose is sufficient to treat or ameliorate symptoms or signs of disease without producing unacceptable toxicity to the subject. Systemic or local administration can be utilized.

In the context of nucleic acid vaccines, naturally occurring or synthetic immunostimulatory compositions that bind to and stimulate receptors involved in innate immunity can be administered along with nucleic acid constructs encoding the gp120 polypeptides. For example, agents that stimulate certain Toll-like receptors (such as TLR7, TLR8 and TLR9) can be administered in combination with the nucleic acid constructs encoding gp120 polypeptides. In some embodiments, the nucleic acid construct is administered in combination with immunostimulatory CpG oligonucleotides.

Nucleic acid constructs encoding gp120 polypeptides can be introduced in vivo as naked DNA plasmids. DNA vectors can be introduced into the desired host cells by methods known in the art, including but not limited to transfection, electroporation (for example, transcutaneous electroporation), microinjection, transduction, cell fusion, DEAE dextran, calcium phosphate precipitation, use of a gene gun, or use of a DNA vector transporter (See for example, Wu et al. J. Biol. Chem., 267:963-967, 1992; Wu and Wu J. Biol. Chem., 263:14621-14624, 1988; and Williams et al. Proc. Natl. Acad. Sci. USA 88:2726-2730, 1991). As described in detail in the Examples, a needleless delivery device, such as a BIOJECTOR® needleless injection device can be utilized to introduce the therapeutic nucleic acid constructs in vivo. Receptor-mediated DNA delivery approaches can also be used (Curiel et al. Hum. Gene Ther., 3:147-154, 1992; and Wu and Wu, J. Biol. Chem., 262:4429-4432, 1987). Methods for formulating and administering naked DNA to mammalian muscle tissue are disclosed in U.S. Pat. Nos. 5,580,859 and 5,589,466, both of which are herein incorporated by reference. Other molecules are also useful for facilitating transfection of a nucleic acid in vivo, such as a cationic oligopeptide (for example, WO95/21931), peptides derived from DNA binding proteins (for example, WO96/25508), or a cationic polymer (for example, WO95/21931).

Another well known method that can be used to introduce nucleic acid constructs encoding gp120 immunogens into host cells is particle bombardment (also know as biolistic transformation). Biolistic transformation is commonly accomplished in one of several ways. One common method involves propelling inert or biologically active particles at cells. This technique is disclosed in, for example, U.S. Pat. Nos. 4,945,050, 5,036,006; and 5,100,792, all to Sanford et al., which are hereby incorporated by reference. Generally, this procedure involves propelling inert or biologically active particles at the cells under conditions effective to penetrate the outer surface of the cell and to be incorporated within the interior thereof. When inert particles are utilized, the plasmid can be introduced into the cell by coating the particles with the plasmid containing the exogenous DNA. Alternatively, the target cell can be surrounded by the plasmid so that the plasmid is carried into the cell by the wake of the particle.

Alternatively, the vector can be introduced in vivo by lipofection. For the past decade, there has been increasing use of liposomes for encapsulation and transfection of nucleic acids in vitro. Synthetic cationic lipids designed to limit the difficulties and dangers encountered with liposome mediated transfection can be used to prepare liposomes for in vivo transfection of a gene encoding a marker (Felgner et. al. Proc. Natl. Acad. Sci. USA 84:7413-7417, 1987; Mackey, et al. Proc. Natl. Acad. Sci. USA 85:8027-8031, 1988; Ulmer et al. Science 259:1745-1748, 1993). The use of cationic lipids can promote encapsulation of negatively charged nucleic acids, and also promote fusion with negatively charged cell membranes (Felgner and Ringold Science 337:387-388, 1989). Particularly useful lipid compounds and compositions for transfer of nucleic acids are described in WO95/18863 and WO96/17823, and in U.S. Pat. No. 5,459,127, herein incorporated by reference.

As with the immunogenic polypeptide, the nucleic acid compositions may be administered in a single dose, or multiple doses separated by a time interval can be administered to elicit an immune response against HIV. For example, two doses, or three doses, or four doses, or five doses, or six doses or more can be administered to a subject over a period of several weeks, several months or even several years, to optimize the immune response.

It may be advantageous to administer the immunogenic compositions disclosed herein with other agents such as proteins, peptides, antibodies, and other anti-HIV agents. Examples of such anti-HIV therapeutic agents include nucleoside reverse transcriptase inhibitors, such as abacavir, AZT, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zalcitabine, zidovudine, and the like, non-nucleoside reverse transcriptase inhibitors, such as delavirdine, efavirenz, nevirapine, protease inhibitors such as amprenavir, atazanavir, indinavir, lopinavir, nelfinavir osamprenavir, ritonavir, saquinavir, tipranavir, and the like, and fusion protein inhibitors such as enfuvirtide and the like. In certain embodiments, immunonogenic compositions are administered concurrently with other anti-HIV therapeutic agents. In certain embodiments, the immunonogenic compositions are administered sequentially with other anti-HIV therapeutic agents, such as before or after the other agent. One of ordinary skill in the art would know that sequential administration can mean immediately following or after an appropriate period of time, such as hours days, weeks, months, or even years later.

While not being bound by theory, it is believed that CD4 binding to gp120 triggers the exposure of the immunodominant V3 loop. Thus, co-administration of soluble forms of CD4, such as the fragments described herein, or an antibody that binds to the CD4 binding site, can lead to enhanced elicitation of an immunogenic response to gp120.

In certain embodiments, immunonogenic compositions disclosed herein are administered with a soluble portion of CD4, for example a sufficient portion of the CD4 to bind to the CD4 binding site on gp120. Such soluble fragments typically include both the D1 and D2 extracellular domains of CD4 (D1D2) or sCD4 (which is comprised of D1 D2 D3 and D4 domains of CD4), although smaller fragments may also provide specific and functional CD4-like binding. In certain embodiments, the gp120 polypeptide with an extended V3 loop or a nucleic acid encoding the same is administered concurrently with a soluble portion of CD4. In other embodiments, the gp120 polypeptide with an extended V3 loop or a nucleic acid encoding the same is administered concurrently with an antibody that binds to the CD4 binding site on gp120.

The immunogenic gp120 polypeptides and nucleic acid encoding these polypeptides (such as stabilized gp120 polypeptides, gp120 polypeptides with an extended V3 loop) can be used in a novel multistep immunization regime. Typically, this regime includes administering to a subject a therapeutically effective amount of a gp120 polypeptide as disclosed herein (the prime) and boosting the immunogenic response with stabilized gp140 trimer (Yang et al. J. Virol. 76(9):4634-42, 2002) after an appropriate period of time. The method of eliciting such an immune reaction is what is known as “prime-boost.” In this method, a gp120 polypeptide is initially administered to a subject and at periodic times thereafter stabilized gp140 trimer boosts are administered. Examples of stabilized gp140 or gp120 trimers can be found for example in U.S. Pat. No. 6,911,205 which is incorporated herein in its entirely.

The prime can be administered as a single dose or multiple doses, for example two doses, three doses, four doses, five doses, six doses or more can be administered to a subject over day week or months. The boost can be administered as a single dose or multiple doses, for example two to six doses, or more can be administered to a subject over a day, a week or months. Multiple boosts can also be given, such one to five, or more.

The boosts can be an identical molecule or a somewhat different, but related, molecule. For example, one preferred strategy with the gp120 polypeptides of the present disclosure would be to prime using a stabilized gp120 polypeptide or a gp120 polypeptide with an extended V3 and boosting periodically with stabilized trimers where the gp120 units are designed to come closer and closer to the wild type gp120 over the succession of boosts. For example, the first prime could be a stabilized gp120 polypeptide, with a boost by a stabilized trimer form with the same stabilized gp120 or a trimer with less deletions or changes from the native gp120 conformation, with subsequent boosts using trimers that had still less deletions or changes from the native gp120 conformation until the boosts were finally being given by trimers with a gp120 portion based on the native wild type HIV gp120.

One can also use cocktails containing a variety of different HIV strains to prime and boost with trimers from a variety of different HIV strains or with trimers that are a mixture of multiple HIV strains. For example, the first prime could be with a gp120 polypeptide from one primary HIV isolate, with subsequent boosts using trimers from different primary isolates.

In certain embodiments, the prime is a nucleic acid construct comprising a nucleic acid sequence encoding a gp120 immunogen as disclosed herein, for example an nucleotide sequence encoding the amino acid sequence set forth as SEQ ID NO: 1 or SEQ ID NO: 2, or the nucleotide sequence as set forth as on of SEQ ID NO: 4-18 or a degenerate variant thereof. In certain embodiments the boost comprises a nucleic acid sequence encoding a stabilized gp140 trimer.

V. Crystal Structures

The stabilized gp120 polypeptides and the gp120 polypeptides with an extended V3 loop disclosed herein can be used to produce detailed models of gp120 polypeptide atomic structure. Exemplary coordinate data is given in Table 1 and Table 2. The atomic coordinate data is disclosed herein, or the coordinate data derived from homologous proteins may be used to build a three-dimensional model of a gp120 polypeptide or a portion thereof, for example by providing a sufficient number of atoms of the stabilized form of gp120 or the gp120 with the V3 loop in the extended conformation as defined by the coordinates of Table 1 or Table 2 which represent a surface or three-dimensional region of interest, such as an antigenic surface or ligand binding site. Thus, there can be provided the coordinates of at least about 5, such at least about 10, at least about 20, at least about 30, at least at least about 40, at least about 50, at least about 60, at least about 70, at least about 80, at least about 90, at least about 100, at least about 150, at least about 200, at least about 250, at least about 300, at least about 350, at least about 400, at least about 450, at least about 500 or more atoms of the structure, such as defined by the coordinates of Table 1 or Table 2. Thus, a sub-domain, region, or fragment of interest of the stabilized form of gp120 or the gp120 with the extended V3 loop which is in the vicinity of the antigenic surface, can be provided for identifying or rationally designing a compound or drug, such as an immunogen. A “sub-domain,” “region,” or “fragment” can mean at least one, for example, one, two, three, four, or more, element(s) of secondary structure of particular regions of the stabilized form of gp120 or the gp120 with the extended V3 loop gp120 with the extended V3 loop, and includes those set forth in Table 1 and Table 2.

Any available computational methods may be used to build the three dimensional model. As a starting point, the X-ray diffraction pattern obtained from the assemblage of the molecules or atoms in a crystalline version of a gp120 polypeptide can be used to build an electron density map using tools well known to those skilled in the art of crystallography and X-ray diffraction techniques. Additional phase information extracted either from the diffraction data and available in the published literature and/or from supplementing experiments may then used to complete the reconstruction.

For an overview of the procedures of collecting, analyzing, and utilizing X-ray diffraction data for the construction of electron densities see, for example, Campbell et al., Biological Spectioscopy, The Benjamin/Cummings Publishing Co., Inc., Menlo Park, Calif., 1984; Cantor et al., Biophysical Chemistry, Part II: Techniques for the study of biological structure and function, W.H. Freeman and Co., San Francisco, Calif. 1980; A. T. Brunger, X-plor Version 3.1: A system for X-ray crystallography and NMR, Yale Univ. Pr., New Haven, Conn. 1993; M. M. Woolfson, An Introduction to X-ray Crystallography, Cambridge Univ. Pr., Cambridge, UK, 1997; J. Drenth, Principles of Protein X-ray Crystallography (Springer Advanced Texts in Chemistry), Springer Verlag; Berlin, 1999; Tsirelson et al, Electron Density and Bonding in Crystals: Principles, Theory and X-ray Diffraction Experiments in Solid State Physics and Chemistry, Inst. of Physics Pub., 1996; each of which is herein specifically incorporated by reference in their entirety.

Information on molecular modeling can be found for example in, M. Schlecht, Molecular Modeling on the PC, 1998, John Wiley & Sons; Gans et al., Fundamental Principals of Molecular Modeling, Plenum Pub. Corp., 1996; N. C. Cohen (editor), Guidebook on Molecular Modeling in Drug Design, Academic Press, 1996; and W. B. Smith, Introduction to Theoretical Organic Chemistry and Molecular Modeling, 1996.

Typically, a well-ordered crystal that will diffract x-rays strongly is used to solve the three-dimensional structure of a protein by x-ray crystallography. The crystallographic method directs a beam of x-rays onto a regular, repeating array of many identical molecules. The x-rays are diffracted from it in a pattern from which the atomic positions of the atom that make up the molecule of interest can be determined.

Substantially pure and homogeneous protein samples are usually used for crystallization. Typically, crystals form when molecules are precipitated very slowly from supersaturated solutions. A typical procedure for making protein crystals is the hanging-drop method, in which a drop of protein solution is brought very gradually to supersaturation by loss of water from the droplet to the larger reservoir that contains salt, polyethylene glycol, or other solution that functions as a hydroattractant, although any other method that generates diffraction quality crystals can be used. In some examples diffraction quality crystals are obtained by seeding the supersaturated solution with smaller crystals that serve as templates.

Powerful x-ray beams can be produced from synchrotron storage rings where electrons (or positrons) travel close to the speed of light. These particles emit very strong radiation at all wavelengths from short gamma rays to visible light. When used as an x-ray source, only radiation within a window of suitable wavelengths is channeled from the storage ring.

In diffraction experiments a narrow and parallel beam of x-rays is taken out from the x-ray source and directed onto the crystal to produce diffracted beams. The incident x-ray beam causes damage to both protein and solvent molecules. The crystal is, therefore, usually cooled to prolong its lifetime (for example to −220° to −50° C.). In some examples, single crystals are used to obtain a data set, while in other examples, multiple crystals are used to obtain a data set. The x-ray beam must strike the crystal from many different directions to produce all possible diffraction spots, thereby creating a complete data set. Therefore, the crystal is rotated relative to the beam during data collection. The diffracted spots are recorded either on a film, or by an electronic detector, both of which are commercially available.

When the primary beam from an x-ray source strikes the crystal, x-rays interact with the electrons on each atom in the crystal and cause them to oscillate. The oscillating electrons serve as a new source of x-rays, which are emitted in almost all directions in a process referred to as scattering. When atoms (and hence their electrons) are arranged in a regular three-dimensional array, as in a crystal, the x-rays emitted from the oscillating electrons interfere with one another. In most cases, these x-rays, colliding from different directions, cancel each other out; those from certain directions, however, will add together to produce diffracted beams of radiation that can be recorded as a pattern on a photographic plate or detector.

The diffraction pattern obtained in an x-ray experiment is related to the crystal that caused the diffraction. X-rays that are reflected from adjacent planes travel different distances, and diffraction only occurs when the difference in distance is equal to the wavelength of the x-ray beam. This distance is dependent on the reflection angle, which is equal to the angle between the primary beam and the planes.

Each atom in a crystal scatters x-rays in all directions, and only those that positively interfere with one another, according to Bragg's law (2d sin θ=λ), give rise to diffracted beams that can be recorded as a distinct diffraction spot above background. Each diffraction spot is the result of interference of all x-rays with the same diffraction angle emerging from all atoms. To extract information about individual atoms from such a system requires considerable computation. The mathematical tool that is used to handle such problems is called the Fourier transform.

Each diffracted beam, which is recorded as a spot on the film, is defined by three properties: the amplitude, which is measured as the intensity of the spot; the wavelength, which is determined by the x-ray source; and the phase information, which is lost in x-ray experiments and must be calculated. All three properties are used for all of the diffracted beams, in order to determine the position of the atoms giving rise to the diffracted beams. Methods of determining the phases are well know in the art.

For example, phase differences between diffracted spots can be determined from intensity changes following heavy atom derivatization. Another example would be determining the phases by molecular replacement.

The amplitudes and the phases of the diffraction data from the protein crystals are used to calculate an electron-density map of the repeating unit of the crystal. A model of the particular amino acid sequence is built to approximate the electron density map.

The initial model will contain some errors. Provided the protein crystals diffract to high enough resolution (e.g., better than 3.5 Å), most or substantially all of the errors can be removed by crystallographic refinement of the model using computer algorithms. In this process, the model is changed to minimize the difference between the experimentally observed diffraction amplitudes and those calculated for a hypothetical crystal containing the model. This difference is expressed as an R factor (residual disagreement) which is 0.0 for exact agreement and about 0.59 for total disagreement.

Typically, the R factor of a refined model is preferably between 0.15 and 0.35 (such as less than about 0.24-0.28) for a well-determined protein structure. The residual difference is a consequence of errors and imperfections in the data. These derive from various sources, including slight variations in the conformation of the protein molecules, as well as inaccurate corrections both for the presence of solvent and for differences in the orientation of the microcrystals from which the crystal is built. Thus, the final model represents an average of molecules that are slightly different in both conformation and orientation.

In refined structures at high resolution, there are usually no major errors in the orientation of individual residues, and the estimated errors in atomic positions are usually around 0.1-0.2 Å, provided the amino acid sequence is known.

Most x-ray structures are determined to a resolution between 1.7 Å. and 3.5 Å. Electron-density maps with this resolution range are preferably interpreted by fitting the known amino acid sequences into regions of electron density in which individual atoms are not resolved.

VI. Crystals Structure of Stabilized gp120

The present disclosure also relates to the crystals obtained from stabilized forms of gp120, the crystal structures of the stabilized forms of gp120, the three-dimensional coordinates of the stabilized forms of gp120 polypeptide and three-dimensional structures of models of stabilized forms of gp120. Table 1 provides the atomic coordinates of the crystal structure of the polypeptide encoded by SEQ ID NO: 14.

TABLE 1 The structural coordinates of an exemplary stabilized form of gp120 at atomic resolution ATOM 1 CB GLU 83 18.617 −44.257 86.334 1.00 108.57 ATOM 2 CG GLU 83 17.192 −44.735 86.515 1.00 108.41 ATOM 3 CD GLU 83 16.205 −43.880 85.755 1.00 108.12 ATOM 4 OE1 GLU 83 16.358 −43.762 84.524 1.00 108.57 ATOM 5 OE2 GLU 83 15.280 −43.327 86.385 1.00 107.50 ATOM 6 C GLU 83 19.772 −46.457 86.717 1.00 109.62 ATOM 7 O GLU 83 18.985 −47.321 87.117 1.00 110.00 ATOM 8 N GLU 83 20.954 −44.298 87.129 1.00 108.79 ATOM 9 CA GLU 83 19.642 −45.003 87.189 1.00 109.16 ATOM 10 N VAL 84 20.768 −46.714 85.869 1.00 109.52 ATOM 11 CA VAL 84 21.044 −48.053 85.341 1.00 109.11 ATOM 12 CB VAL 84 20.172 −48.376 84.093 1.00 108.87 ATOM 13 CG1 VAL 84 18.713 −48.542 84.498 1.00 108.27 ATOM 14 CG2 VAL 84 20.302 −47.271 83.061 1.00 109.39 ATOM 15 C VAL 84 22.526 −48.185 84.964 1.00 108.77 ATOM 16 O VAL 84 22.925 −47.846 83.851 1.00 108.35 ATOM 17 N VAL 85 23.332 −48.684 85.900 1.00 108.71 ATOM 18 CA VAL 85 24.774 −48.848 85.689 1.00 108.45 ATOM 19 CB VAL 85 25.515 −49.032 87.038 1.00 108.05 ATOM 20 CG1 VAL 85 25.521 −47.724 87.807 1.00 108.41 ATOM 21 CG2 VAL 85 24.837 −50.110 87.862 1.00 107.81 ATOM 22 C VAL 85 25.175 −49.994 84.754 1.00 108.29 ATOM 23 O VAL 85 24.757 −51.138 84.941 1.00 108.64 ATOM 24 N LEU 86 25.997 −49.670 83.755 1.00 107.51 ATOM 25 CA LEU 86 26.483 −50.644 82.774 1.00 106.03 ATOM 26 CB LEU 86 26.839 −49.943 81.458 1.00 104.36 ATOM 27 CG LEU 86 25.737 −49.391 80.552 1.00 103.07 ATOM 28 CD1 LEU 86 24.750 −48.544 81.333 1.00 102.61 ATOM 29 CD2 LEU 86 26.390 −48.575 79.450 1.00 101.71 ATOM 30 C LEU 86 27.720 −51.369 83.298 1.00 105.81 ATOM 31 O LEU 86 28.354 −50.916 84.254 1.00 105.88 ATOM 32 N VAL 87 28.065 −52.490 82.668 1.00 105.43 ATOM 33 CA VAL 87 29.231 −53.263 83.083 1.00 104.73 ATOM 34 CB VAL 87 28.827 −54.553 83.805 1.00 104.68 ATOM 35 CG1 VAL 87 28.000 −54.214 85.032 1.00 104.54 ATOM 36 CG2 VAL 87 28.057 −55.462 82.857 1.00 105.03 ATOM 37 C VAL 87 30.119 −53.643 81.910 1.00 104.29 ATOM 38 O VAL 87 29.635 −53.933 80.813 1.00 103.86 ATOM 39 N ASN 88 31.425 −53.652 82.166 1.00 104.01 ATOM 40 CA ASN 88 32.428 −53.982 81.155 1.00 103.78 ATOM 41 CB ASN 88 32.360 −55.474 80.781 1.00 104.65 ATOM 42 CG ASN 88 32.859 −56.393 81.902 1.00 105.20 ATOM 43 OD1 ASN 88 33.953 −56.199 82.445 1.00 104.86 ATOM 44 ND2 ASN 88 32.056 −57.399 82.235 1.00 104.99 ATOM 45 C ASN 88 32.252 −53.117 79.909 1.00 102.44 ATOM 46 O ASN 88 32.505 −53.561 78.787 1.00 101.94 ATOM 47 N VAL 89 31.822 −51.875 80.122 1.00 100.88 ATOM 48 CA VAL 89 31.614 −50.931 79.032 1.00 98.81 ATOM 49 CB VAL 89 30.231 −50.258 79.127 1.00 98.28 ATOM 50 CG1 VAL 89 30.035 −49.322 77.953 1.00 97.33 ATOM 51 CG2 VAL 89 29.139 −51.310 79.151 1.00 98.08 ATOM 52 C VAL 89 32.679 −49.841 79.051 1.00 97.94 ATOM 53 O VAL 89 33.180 −49.461 80.113 1.00 97.43 ATOM 54 N THR 90 33.020 −49.348 77.864 1.00 96.73 ATOM 55 CA THR 90 34.020 −48.295 77.724 1.00 95.18 ATOM 56 CB THR 90 35.403 −48.891 77.319 1.00 95.36 ATOM 57 OG1 THR 90 36.380 −47.845 77.263 1.00 95.05 ATOM 58 CG2 THR 90 35.324 −49.591 75.962 1.00 95.57 ATOM 59 C THR 90 33.551 −47.260 76.686 1.00 93.85 ATOM 60 O THR 90 33.505 −47.539 75.481 1.00 93.47 ATOM 61 N GLU 91 33.196 −46.069 77.177 1.00 91.35 ATOM 62 CA GLU 91 32.707 −44.963 76.347 1.00 87.86 ATOM 63 CB GLU 91 31.343 −44.504 76.865 1.00 88.15 ATOM 64 CG GLU 91 30.189 −44.701 75.899 1.00 89.11 ATOM 65 CD GLU 91 30.231 −43.732 74.737 1.00 90.17 ATOM 66 OE1 GLU 91 29.248 −43.679 73.968 1.00 90.39 ATOM 67 OE2 GLU 91 31.249 −43.023 74.591 1.00 90.88 ATOM 68 C GLU 91 33.676 −43.781 76.358 1.00 85.11 ATOM 69 O GLU 91 34.317 −43.509 77.369 1.00 85.37 ATOM 70 N ASN 92 33.783 −43.076 75.235 1.00 81.78 ATOM 71 CA ASN 92 34.683 −41.928 75.151 1.00 78.41 ATOM 72 CB ASN 92 35.342 −41.832 73.778 1.00 79.10 ATOM 73 CG ASN 92 36.358 −42.903 73.549 1.00 79.88 ATOM 74 OD1 ASN 92 36.973 −43.404 74.492 1.00 80.64 ATOM 75 ND2 ASN 92 36.568 −43.252 72.285 1.00 80.59 ATOM 76 C ASN 92 34.001 −40.602 75.405 1.00 75.77 ATOM 77 O ASN 92 33.114 −40.198 74.650 1.00 75.80 ATOM 78 N PHE 93 34.426 −39.915 76.455 1.00 71.82 ATOM 79 CA PHE 93 33.870 −38.608 76.751 1.00 68.48 ATOM 80 CB PHE 93 33.622 −38.429 78.244 1.00 67.44 ATOM 81 CG PHE 93 32.495 −39.245 78.781 1.00 67.39 ATOM 82 CD1 PHE 93 32.554 −40.629 78.775 1.00 68.23 ATOM 83 CD2 PHE 93 31.396 −38.629 79.358 1.00 68.44 ATOM 84 CE1 PHE 93 31.537 −41.393 79.346 1.00 68.02 ATOM 85 CE2 PHE 93 30.373 −39.382 79.931 1.00 69.14 ATOM 86 CZ PHE 93 30.446 −40.768 79.926 1.00 68.02 ATOM 87 C PHE 93 34.888 −37.568 76.319 1.00 66.64 ATOM 88 O PHE 93 36.094 −37.801 76.418 1.00 66.70 ATOM 89 N ASN 94 34.405 −36.436 75.821 1.00 63.67 ATOM 90 CA ASN 94 35.277 −35.344 75.439 1.00 61.19 ATOM 91 CB ASN 94 35.618 −35.387 73.950 1.00 61.27 ATOM 92 CG ASN 94 36.609 −34.300 73.550 1.00 61.92 ATOM 93 OD1 ASN 94 37.602 −34.062 74.241 1.00 61.52 ATOM 94 ND2 ASN 94 36.351 −33.647 72.422 1.00 61.78 ATOM 95 C ASN 94 34.442 −34.119 75.767 1.00 59.74 ATOM 96 O ASN 94 33.882 −33.482 74.893 1.00 60.53 ATOM 97 N TRP 95 34.345 −33.831 77.055 1.00 57.77 ATOM 98 CA TRP 95 33.579 −32.719 77.567 1.00 55.79 ATOM 99 CB TRP 95 33.948 −32.471 79.030 1.00 53.78 ATOM 100 CG TRP 95 35.277 −31.803 79.223 1.00 49.89 ATOM 101 CD2 TRP 95 35.534 −30.615 79.971 1.00 50.17 ATOM 102 CE2 TRP 95 36.913 −30.357 79.903 1.00 49.60 ATOM 103 CE3 TRP 95 34.727 −29.734 80.707 1.00 50.04 ATOM 104 CD1 TRP 95 36.474 −32.211 78.737 1.00 49.33 ATOM 105 NE1 TRP 95 37.468 −31.354 79.134 1.00 49.08 ATOM 106 CZ2 TRP 95 37.513 −29.263 80.533 1.00 49.33 ATOM 107 CZ3 TRP 95 35.316 −28.650 81.335 1.00 49.36 ATOM 108 CH2 TRP 95 36.696 −28.424 81.246 1.00 50.29 ATOM 109 C TRP 95 33.733 −31.432 76.782 1.00 55.51 ATOM 110 O TRP 95 32.832 −30.588 76.793 1.00 55.05 ATOM 111 N CYS 96 34.876 −31.286 76.114 1.00 55.79 ATOM 112 CA CYS 96 35.183 −30.109 75.309 1.00 56.39 ATOM 113 C CYS 96 34.565 −30.210 73.922 1.00 55.35 ATOM 114 O CYS 96 35.144 −29.765 72.935 1.00 55.34 ATOM 115 CB CYS 96 36.705 −29.935 75.183 1.00 59.56 ATOM 116 SG CYS 96 37.516 −29.511 76.772 1.00 65.71 ATOM 117 N LYS 97 33.370 −30.781 73.863 1.00 54.38 ATOM 118 CA LYS 97 32.641 −30.968 72.619 1.00 53.06 ATOM 119 CB LYS 97 33.439 −31.832 71.655 1.00 54.39 ATOM 120 CG LYS 97 34.407 −31.101 70.750 1.00 57.02 ATOM 121 CD LYS 97 35.090 −32.103 69.834 1.00 59.38 ATOM 122 CE LYS 97 36.181 −31.488 68.980 1.00 60.34 ATOM 123 NZ LYS 97 36.872 −32.554 68.187 1.00 60.06 ATOM 124 C LYS 97 31.366 −31.691 72.967 1.00 52.61 ATOM 125 O LYS 97 31.042 −32.698 72.363 1.00 53.46 ATOM 126 N ASN 98 30.653 −31.195 73.965 1.00 52.56 ATOM 127 CA ASN 98 29.410 −31.833 74.362 1.00 52.14 ATOM 128 CB ASN 98 29.300 −31.911 75.889 1.00 50.77 ATOM 129 CG ASN 98 28.087 −32.706 76.342 1.00 49.63 ATOM 130 OD1 ASN 98 26.961 −32.405 75.957 1.00 48.41 ATOM 131 ND2 ASN 98 28.314 −33.723 77.168 1.00 48.49 ATOM 132 C ASN 98 28.232 −31.056 73.788 1.00 52.73 ATOM 133 O ASN 98 28.181 −29.825 73.873 1.00 52.21 ATOM 134 N ASP 99 27.286 −31.780 73.202 1.00 53.95 ATOM 135 CA ASP 99 26.107 −31.160 72.601 1.00 55.38 ATOM 136 CB ASP 99 25.354 −32.184 71.745 1.00 58.50 ATOM 137 CG ASP 99 25.615 −32.009 70.253 1.00 60.48 ATOM 138 OD1 ASP 99 25.206 −32.892 69.462 1.00 61.59 ATOM 139 OD2 ASP 99 26.222 −30.982 69.877 1.00 61.09 ATOM 140 C ASP 99 25.142 −30.546 73.608 1.00 54.26 ATOM 141 O ASP 99 24.342 −29.676 73.260 1.00 54.68 ATOM 142 N MET 100 25.208 −31.008 74.851 1.00 51.85 ATOM 143 CA MET 100 24.331 −30.496 75.889 1.00 49.13 ATOM 144 CB MET 100 24.357 −31.424 77.094 1.00 48.72 ATOM 145 CG MET 100 24.159 −32.873 76.743 1.00 49.12 ATOM 146 SD MET 100 24.699 −33.947 78.077 1.00 48.08 ATOM 147 CE MET 100 23.233 −33.971 79.064 1.00 49.17 ATOM 148 C MET 100 24.783 −29.110 76.308 1.00 47.86 ATOM 149 O MET 100 23.969 −28.274 76.678 1.00 48.48 ATOM 150 N VAL 101 26.085 −28.867 76.253 1.00 46.25 ATOM 151 CA VAL 101 26.616 −27.569 76.641 1.00 45.39 ATOM 152 CB VAL 101 28.145 −27.522 76.472 1.00 45.11 ATOM 153 CG1 VAL 101 28.654 −26.126 76.755 1.00 44.71 ATOM 154 CG2 VAL 101 28.801 −28.517 77.401 1.00 43.94 ATOM 155 C VAL 101 25.994 −26.455 75.800 1.00 45.33 ATOM 156 O VAL 101 25.579 −25.426 76.318 1.00 45.54 ATOM 157 N GLU 102 25.918 −26.676 74.498 1.00 45.19 ATOM 158 CA GLU 102 25.371 −25.685 73.599 1.00 46.23 ATOM 159 CB GLU 102 25.770 −26.016 72.167 1.00 49.62 ATOM 160 CG GLU 102 27.168 −26.621 72.070 1.00 55.61 ATOM 161 CD GLU 102 28.245 −25.679 72.588 1.00 59.03 ATOM 162 OE1 GLU 102 29.297 −26.166 73.077 1.00 59.85 ATOM 163 OE2 GLU 102 28.034 −24.448 72.489 1.00 60.10 ATOM 164 C GLU 102 23.869 −25.627 73.715 1.00 45.67 ATOM 165 O GLU 102 23.278 −24.568 73.567 1.00 45.84 ATOM 166 N GLN 103 23.244 −26.764 73.982 1.00 45.79 ATOM 167 CA GLN 103 21.795 −26.786 74.101 1.00 47.31 ATOM 168 CB GLN 103 21.271 −28.220 74.156 1.00 48.93 ATOM 169 CG GLN 103 19.750 −28.313 74.345 1.00 52.63 ATOM 170 CD GLN 103 18.929 −27.662 73.216 1.00 53.89 ATOM 171 OE1 GLN 103 17.703 −27.566 73.309 1.00 54.70 ATOM 172 NE2 GLN 103 19.600 −27.222 72.154 1.00 52.85 ATOM 173 C GLN 103 21.416 −26.066 75.363 1.00 47.02 ATOM 174 O GLN 103 20.494 −25.260 75.390 1.00 46.84 ATOM 175 N MET 104 22.146 −26.369 76.418 1.00 48.58 ATOM 176 CA MET 104 21.902 −25.752 77.703 1.00 49.89 ATOM 177 CB MET 104 22.985 −26.182 78.694 1.00 52.33 ATOM 178 CG MET 104 22.741 −25.743 80.137 1.00 56.81 ATOM 179 SD MET 104 22.286 −27.119 81.216 1.00 60.04 ATOM 180 CE MET 104 20.594 −27.574 80.517 1.00 58.09 ATOM 181 C MET 104 21.975 −24.255 77.483 1.00 49.53 ATOM 182 O MET 104 20.998 −23.535 77.676 1.00 50.52 ATOM 183 N HIS 105 23.146 −23.808 77.048 1.00 48.30 ATOM 184 CA HIS 105 23.409 −22.403 76.807 1.00 47.10 ATOM 185 CB HIS 105 24.712 −22.250 76.031 1.00 46.50 ATOM 186 CG HIS 105 25.181 −20.836 75.913 1.00 45.38 ATOM 187 CD2 HIS 105 25.468 −20.082 74.828 1.00 44.97 ATOM 188 ND1 HIS 105 25.431 −20.044 77.010 1.00 45.09 ATOM 189 CE1 HIS 105 25.855 −18.859 76.607 1.00 45.28 ATOM 190 NE2 HIS 105 25.887 −18.858 75.289 1.00 45.84 ATOM 191 C HIS 105 22.306 −21.664 76.077 1.00 47.03 ATOM 192 O HIS 105 22.185 −20.458 76.222 1.00 47.98 ATOM 193 N GLU 106 21.506 −22.362 75.283 1.00 47.46 ATOM 194 CA GLU 106 20.439 −21.680 74.564 1.00 48.81 ATOM 195 CB GLU 106 20.203 −22.323 73.203 1.00 51.42 ATOM 196 CG GLU 106 21.432 −22.305 72.320 1.00 57.65 ATOM 197 CD GLU 106 21.126 −22.632 70.870 1.00 61.26 ATOM 198 OE1 GLU 106 20.441 −23.656 70.619 1.00 63.05 ATOM 199 OE2 GLU 106 21.583 −21.866 69.985 1.00 62.41 ATOM 200 C GLU 106 19.153 −21.679 75.356 1.00 48.72 ATOM 201 O GLU 106 18.369 −20.731 75.281 1.00 47.67 ATOM 202 N ASP 107 18.928 −22.747 76.109 1.00 49.07 ATOM 203 CA ASP 107 17.733 −22.828 76.921 1.00 49.88 ATOM 204 CB ASP 107 17.606 −24.210 77.535 1.00 52.08 ATOM 205 CG ASP 107 17.469 −25.283 76.484 1.00 55.84 ATOM 206 OD1 ASP 107 16.638 −25.099 75.569 1.00 56.69 ATOM 207 OD2 ASP 107 18.186 −26.304 76.566 1.00 58.55 ATOM 208 C ASP 107 17.834 −21.775 78.000 1.00 49.32 ATOM 209 O ASP 107 16.845 −21.127 78.340 1.00 50.32 ATOM 210 N ILE 108 19.043 −21.595 78.524 1.00 48.00 ATOM 211 CA ILE 108 19.285 −20.600 79.562 1.00 46.04 ATOM 212 CB ILE 108 20.713 −20.686 80.102 1.00 45.64 ATOM 213 CG2 ILE 108 20.891 −19.691 81.234 1.00 43.75 ATOM 214 CG1 ILE 108 21.024 −22.119 80.550 1.00 46.19 ATOM 215 CD1 ILE 108 20.330 −22.579 81.803 1.00 46.61 ATOM 216 C ILE 108 19.082 −19.204 78.979 1.00 45.89 ATOM 217 O ILE 108 18.185 −18.483 79.396 1.00 47.43 ATOM 218 N CYS 109 19.913 −18.824 78.015 1.00 44.32 ATOM 219 CA CYS 109 19.773 −17.518 77.413 1.00 43.51 ATOM 220 C CYS 109 18.334 −17.218 77.154 1.00 41.47 ATOM 221 O CYS 109 17.860 −16.135 77.471 1.00 40.35 ATOM 222 CB CYS 109 20.550 −17.422 76.110 1.00 46.91 ATOM 223 SG CYS 109 22.213 −16.826 76.488 1.00 54.67 ATOM 224 N SER 110 17.643 −18.198 76.585 1.00 41.43 ATOM 225 CA SER 110 16.227 −18.094 76.252 1.00 42.22 ATOM 226 CB SER 110 15.780 −19.377 75.551 1.00 43.14 ATOM 227 OG SER 110 14.365 −19.448 75.485 1.00 46.83 ATOM 228 C SER 110 15.347 −17.839 77.473 1.00 41.93 ATOM 229 O SER 110 14.414 −17.037 77.438 1.00 40.88 ATOM 230 N LEU 111 15.646 −18.534 78.557 1.00 42.29 ATOM 231 CA LEU 111 14.881 −18.369 79.773 1.00 43.38 ATOM 232 CB LEU 111 15.370 −19.376 80.807 1.00 41.89 ATOM 233 CG LEU 111 14.309 −19.802 81.813 1.00 42.18 ATOM 234 CD1 LEU 111 13.052 −20.245 81.083 1.00 42.84 ATOM 235 CD2 LEU 111 14.863 −20.926 82.659 1.00 43.66 ATOM 236 C LEU 111 15.061 −16.935 80.279 1.00 45.09 ATOM 237 O LEU 111 14.095 −16.253 80.633 1.00 44.96 ATOM 238 N TRP 112 16.307 −16.476 80.290 1.00 46.31 ATOM 239 CA TRP 112 16.613 −15.131 80.744 1.00 48.17 ATOM 240 CB TRP 112 18.126 −14.922 80.779 1.00 49.91 ATOM 241 CG TRP 112 18.747 −15.516 82.010 1.00 52.44 ATOM 242 CD2 TRP 112 19.544 −14.840 82.984 1.00 53.45 ATOM 243 CE2 TRP 112 19.851 −15.778 83.999 1.00 53.54 ATOM 244 CE3 TRP 112 20.031 −13.532 83.102 1.00 54.72 ATOM 245 CD1 TRP 112 18.613 −16.796 82.453 1.00 52.57 ATOM 246 NE1 TRP 112 19.269 −16.964 83.647 1.00 51.79 ATOM 247 CZ2 TRP 112 20.619 −15.454 85.121 1.00 55.71 ATOM 248 CZ3 TRP 112 20.797 −13.204 84.217 1.00 56.51 ATOM 249 CH2 TRP 112 21.083 −14.165 85.215 1.00 57.71 ATOM 250 C TRP 112 15.951 −14.044 79.914 1.00 49.45 ATOM 251 O TRP 112 15.497 −13.047 80.459 1.00 50.46 ATOM 252 N ASP 113 15.889 −14.222 78.603 1.00 50.27 ATOM 253 CA ASP 113 15.257 −13.220 77.765 1.00 51.73 ATOM 254 CB ASP 113 15.386 −13.594 76.291 1.00 53.23 ATOM 255 CG ASP 113 16.821 −13.541 75.807 1.00 55.73 ATOM 256 OD1 ASP 113 17.504 −12.529 76.078 1.00 56.27 ATOM 257 OD2 ASP 113 17.270 −14.506 75.152 1.00 57.05 ATOM 258 C ASP 113 13.788 −13.064 78.125 1.00 52.99 ATOM 259 O ASP 113 13.250 −11.953 78.091 1.00 52.81 ATOM 260 N GLN 114 13.144 −14.173 78.483 1.00 54.06 ATOM 261 CA GLN 114 11.727 −14.145 78.837 1.00 54.67 ATOM 262 CB GLN 114 11.018 −15.408 78.318 1.00 56.60 ATOM 263 CG GLN 114 11.793 −16.710 78.507 1.00 61.03 ATOM 264 CD GLN 114 11.135 −17.906 77.812 1.00 63.04 ATOM 265 OE1 GLN 114 10.062 −18.362 78.210 1.00 64.12 ATOM 266 NE2 GLN 114 11.780 −18.411 76.764 1.00 63.49 ATOM 267 C GLN 114 11.441 −13.953 80.321 1.00 53.71 ATOM 268 O GLN 114 10.316 −14.158 80.766 1.00 54.68 ATOM 269 N SER 115 12.449 −13.547 81.086 1.00 52.50 ATOM 270 CA SER 115 12.265 −13.308 82.519 1.00 51.69 ATOM 271 CB SER 115 13.038 −14.336 83.348 1.00 51.04 ATOM 272 OG SER 115 12.621 −15.652 83.056 1.00 52.93 ATOM 273 C SER 115 12.746 −11.913 82.901 1.00 51.57 ATOM 274 O SER 115 12.011 −11.142 83.520 1.00 52.69 ATOM 275 N LEU 116 13.989 −11.604 82.532 1.00 49.90 ATOM 276 CA LEU 116 14.603 −10.315 82.825 1.00 48.45 ATOM 277 CB LEU 116 16.022 −10.529 83.343 1.00 47.47 ATOM 278 CG LEU 116 16.268 −10.161 84.806 1.00 48.17 ATOM 279 CD1 LEU 116 17.715 −10.461 85.176 1.00 47.96 ATOM 280 CD2 LEU 116 15.955 −8.686 85.019 1.00 47.70 ATOM 281 C LEU 116 14.645 −9.431 81.581 1.00 48.28 ATOM 282 O LEU 116 15.644 −9.414 80.858 1.00 48.83 ATOM 283 N LYS 117 13.571 −8.682 81.345 1.00 46.85 ATOM 284 CA LYS 117 13.479 −7.817 80.170 1.00 45.19 ATOM 285 CB LYS 117 12.012 −7.662 79.768 1.00 45.35 ATOM 286 CG LYS 117 11.377 −8.958 79.341 1.00 45.38 ATOM 287 CD LYS 117 9.987 −8.733 78.809 1.00 45.69 ATOM 288 CE LYS 117 9.621 −9.864 77.882 1.00 45.39 ATOM 289 NZ LYS 117 10.704 −10.041 76.876 1.00 44.68 ATOM 290 C LYS 117 14.100 −6.440 80.351 1.00 43.15 ATOM 291 O LYS 117 14.002 −5.846 81.410 1.00 43.84 ATOM 292 N PRO 118 14.764 −5.920 79.315 1.00 41.84 ATOM 293 CD PRO 118 15.467 −6.711 78.301 1.00 41.18 ATOM 294 CA PRO 118 15.377 −4.594 79.428 1.00 42.68 ATOM 295 CB PRO 118 16.611 −4.708 78.532 1.00 41.64 ATOM 296 CG PRO 118 16.852 −6.184 78.446 1.00 41.32 ATOM 297 C PRO 118 14.452 −3.444 78.977 1.00 44.00 ATOM 298 O PRO 118 13.547 −3.631 78.155 1.00 43.14 ATOM 299 N CYS 119 14.688 −2.258 79.528 1.00 44.26 ATOM 300 CA CYS 119 13.911 −1.082 79.177 1.00 45.33 ATOM 301 C CYS 119 14.328 −0.688 77.776 1.00 44.84 ATOM 302 O CYS 119 13.536 −0.157 76.996 1.00 45.02 ATOM 303 CB CYS 119 14.212 0.059 80.148 1.00 48.41 ATOM 304 SG CYS 119 14.000 −0.390 81.904 1.00 55.41 ATOM 305 N VAL 120 15.595 −0.946 77.476 1.00 43.63 ATOM 306 CA VAL 120 16.165 −0.669 76.166 1.00 42.72 ATOM 307 CB VAL 120 16.807 0.719 76.110 1.00 40.94 ATOM 308 CG1 VAL 120 17.494 0.914 74.784 1.00 38.51 ATOM 309 CG2 VAL 120 15.740 1.773 76.293 1.00 40.48 ATOM 310 C VAL 120 17.217 −1.734 75.897 1.00 43.68 ATOM 311 O VAL 120 17.932 −2.162 76.811 1.00 42.94 ATOM 312 N LYS 121 17.292 −2.168 74.643 1.00 44.39 ATOM 313 CA LYS 121 18.232 −3.197 74.237 1.00 45.78 ATOM 314 CB LYS 121 17.498 −4.530 74.119 1.00 46.75 ATOM 315 CG LYS 121 18.292 −5.667 73.498 1.00 48.39 ATOM 316 CD LYS 121 17.477 −6.942 73.525 1.00 49.47 ATOM 317 CE LYS 121 18.214 −8.075 72.855 1.00 52.19 ATOM 318 NZ LYS 121 17.391 −9.321 72.815 1.00 54.57 ATOM 319 C LYS 121 18.834 −2.829 72.897 1.00 46.81 ATOM 320 O LYS 121 18.119 −2.708 71.913 1.00 47.70 ATOM 321 N LEU 122 20.146 −2.641 72.864 1.00 48.66 ATOM 322 CA LEU 122 20.828 −2.293 71.629 1.00 51.53 ATOM 323 CB LEU 122 21.795 −1.138 71.841 1.00 50.96 ATOM 324 CG LEU 122 21.169 0.187 72.235 1.00 51.52 ATOM 325 CD1 LEU 122 22.202 1.272 72.015 1.00 52.75 ATOM 326 CD2 LEU 122 19.930 0.468 71.403 1.00 51.31 ATOM 327 C LEU 122 21.613 −3.454 71.075 1.00 54.29 ATOM 328 O LEU 122 22.385 −4.069 71.794 1.00 55.82 ATOM 329 N CYS 123 21.422 −3.756 69.796 1.00 57.66 ATOM 330 CA CYS 123 22.156 −4.844 69.161 1.00 61.99 ATOM 331 C CYS 123 22.651 −4.401 67.790 1.00 65.95 ATOM 332 O CYS 123 21.868 −3.977 66.952 1.00 66.42 ATOM 333 CB CYS 123 21.261 −6.068 69.001 1.00 61.14 ATOM 334 SG CYS 123 20.636 −6.863 70.520 1.00 64.65 ATOM 335 N PRO 124 23.962 −4.486 67.543 1.00 70.34 ATOM 336 CD PRO 124 25.032 −4.644 68.538 1.00 71.39 ATOM 337 CA PRO 124 24.526 −4.079 66.255 1.00 74.44 ATOM 338 CB PRO 124 25.915 −3.586 66.640 1.00 73.49 ATOM 339 CG PRO 124 26.298 −4.577 67.678 1.00 72.11 ATOM 340 C PRO 124 24.600 −5.151 65.170 1.00 78.68 ATOM 341 O PRO 124 25.007 −6.289 65.435 1.00 78.97 ATOM 342 N LEU 125 24.216 −4.754 63.952 1.00 83.43 ATOM 343 CA LEU 125 24.246 −5.602 62.755 1.00 87.97 ATOM 344 CB LEU 125 22.826 −5.802 62.199 1.00 85.90 ATOM 345 CG LEU 125 22.682 −6.595 60.892 1.00 85.01 ATOM 346 CD1 LEU 125 23.501 −7.878 60.933 1.00 84.72 ATOM 347 CD2 LEU 125 21.223 −6.908 60.673 1.00 84.26 ATOM 348 C LEU 125 25.136 −4.880 61.723 1.00 91.79 ATOM 349 O LEU 125 24.645 −4.294 60.751 1.00 92.07 ATOM 350 N CYS 126 26.449 −4.932 61.963 1.00 95.81 ATOM 351 CA CYS 126 27.456 −4.274 61.128 1.00 99.93 ATOM 352 C CYS 126 27.478 −4.610 59.639 1.00 101.72 ATOM 353 O CYS 126 26.500 −5.115 59.075 1.00 101.70 ATOM 354 CB CYS 126 28.860 −4.525 61.702 1.00 101.65 ATOM 355 SG CYS 126 29.830 −3.024 62.094 1.00 105.44 ATOM 356 N VAL 127 28.627 −4.317 59.026 1.00 103.91 ATOM 357 CA VAL 127 28.873 −4.528 57.601 1.00 105.90 ATOM 358 CB VAL 127 29.149 −6.029 57.278 1.00 105.47 ATOM 359 CG1 VAL 127 29.583 −6.188 55.822 1.00 104.28 ATOM 360 CG2 VAL 127 30.240 −6.563 58.196 1.00 104.81 ATOM 361 C VAL 127 27.668 −4.011 56.817 1.00 107.53 ATOM 362 O VAL 127 27.187 −2.905 57.086 1.00 107.44 ATOM 363 N GLY 128 27.171 −4.801 55.869 1.00 108.79 ATOM 364 CA GLY 128 26.041 −4.358 55.076 1.00 110.07 ATOM 365 C GLY 128 26.390 −3.033 54.422 1.00 111.37 ATOM 366 O GLY 128 25.543 −2.144 54.318 1.00 111.70 ATOM 367 N ALA 129 27.653 −2.909 54.007 1.00 112.10 ATOM 368 CA ALA 129 28.187 −1.712 53.350 1.00 112.06 ATOM 369 CB ALA 129 27.246 −1.268 52.213 1.00 112.16 ATOM 370 C ALA 129 28.491 −0.520 54.272 1.00 111.66 ATOM 371 O ALA 129 27.895 0.551 54.125 1.00 111.99 ATOM 372 N GLY 194 29.418 −0.709 55.215 1.00 110.69 ATOM 373 CA GLY 194 29.815 0.358 56.129 1.00 108.83 ATOM 374 C GLY 194 28.806 0.894 57.136 1.00 107.51 ATOM 375 O GLY 194 29.136 1.040 58.316 1.00 106.82 ATOM 376 N SER 195 27.596 1.212 56.672 1.00 106.32 ATOM 377 CA SER 195 26.529 1.737 57.529 1.00 104.42 ATOM 378 CB SER 195 25.342 2.211 56.684 1.00 104.28 ATOM 379 OG SER 195 25.728 3.205 55.752 1.00 103.83 ATOM 380 C SER 195 26.050 0.664 58.497 1.00 103.36 ATOM 381 O SER 195 24.927 0.164 58.381 1.00 103.62 ATOM 382 N CYS 196 26.917 0.317 59.446 1.00 101.48 ATOM 383 CA CYS 196 26.631 −0.696 60.461 1.00 98.25 ATOM 384 C CYS 196 25.391 −0.331 61.275 1.00 93.82 ATOM 385 O CYS 196 25.496 0.258 62.352 1.00 93.50 ATOM 386 CB CYS 196 27.846 −0.843 61.390 1.00 100.91 ATOM 387 SG CYS 196 29.301 −1.683 60.659 1.00 104.77 ATOM 388 N ASN 197 24.219 −0.688 60.758 1.00 88.40 ATOM 389 CA ASN 197 22.973 −0.380 61.444 1.00 82.77 ATOM 390 CB ASN 197 21.770 −0.728 60.566 1.00 85.03 ATOM 391 CG ASN 197 21.187 0.494 59.868 1.00 87.21 ATOM 392 OD1 ASN 197 20.801 1.465 60.529 1.00 88.02 ATOM 393 ND2 ASN 197 21.120 0.450 58.539 1.00 88.02 ATOM 394 C ASN 197 22.863 −1.088 62.780 1.00 77.50 ATOM 395 O ASN 197 23.334 −2.210 62.943 1.00 77.29 ATOM 396 N THR 198 22.227 −0.413 63.730 1.00 71.01 ATOM 397 CA THR 198 22.048 −0.929 65.075 1.00 63.96 ATOM 398 CB THR 198 22.715 0.006 66.085 1.00 64.25 ATOM 399 OG1 THR 198 24.118 0.085 65.802 1.00 64.31 ATOM 400 CG2 THR 198 22.496 −0.496 67.500 1.00 64.07 ATOM 401 C THR 198 20.575 −1.056 65.427 1.00 58.97 ATOM 402 O THR 198 19.859 −0.065 65.448 1.00 58.60 ATOM 403 N SER 199 20.136 −2.279 65.709 1.00 53.41 ATOM 404 CA SER 199 18.747 −2.559 66.067 1.00 48.39 ATOM 405 CB SER 199 18.470 −4.051 65.915 1.00 47.89 ATOM 406 OG SER 199 17.306 −4.425 66.627 1.00 48.16 ATOM 407 C SER 199 18.439 −2.134 67.495 1.00 45.34 ATOM 408 O SER 199 19.174 −2.470 68.403 1.00 45.45 ATOM 409 N VAL 200 17.340 −1.414 67.691 1.00 42.99 ATOM 410 CA VAL 200 16.955 −0.932 69.016 1.00 40.63 ATOM 411 CB VAL 200 16.927 0.610 69.046 1.00 39.79 ATOM 412 CG1 VAL 200 16.500 1.098 70.404 1.00 39.65 ATOM 413 CG2 VAL 200 18.290 1.164 68.702 1.00 38.60 ATOM 414 C VAL 200 15.583 −1.440 69.449 1.00 40.29 ATOM 415 O VAL 200 14.629 −1.400 68.678 1.00 40.35 ATOM 416 N ILE 201 15.482 −1.905 70.689 1.00 40.20 ATOM 417 CA ILE 201 14.217 −2.417 71.219 1.00 41.32 ATOM 418 CB ILE 201 14.249 −3.956 71.405 1.00 42.65 ATOM 419 CG2 ILE 201 12.921 −4.441 71.989 1.00 41.02 ATOM 420 CG1 ILE 201 14.543 −4.646 70.070 1.00 43.17 ATOM 421 CD1 ILE 201 14.834 −6.135 70.211 1.00 44.46 ATOM 422 C ILE 201 13.874 −1.810 72.577 1.00 41.94 ATOM 423 O ILE 201 14.654 −1.896 73.532 1.00 41.41 ATOM 424 N THR 202 12.690 −1.214 72.657 1.00 41.95 ATOM 425 CA THR 202 12.226 −0.601 73.889 1.00 42.08 ATOM 426 CB THR 202 11.969 0.892 73.696 1.00 41.25 ATOM 427 OG1 THR 202 13.082 1.490 73.027 1.00 40.91 ATOM 428 CG2 THR 202 11.788 1.560 75.031 1.00 41.52 ATOM 429 C THR 202 10.918 −1.251 74.318 1.00 43.20 ATOM 430 O THR 202 9.948 −1.241 73.563 1.00 43.24 ATOM 431 N GLN 203 10.890 −1.818 75.524 1.00 44.57 ATOM 432 CA GLN 203 9.679 −2.464 76.037 1.00 45.88 ATOM 433 CB GLN 203 9.752 −3.978 75.850 1.00 45.18 ATOM 434 CG GLN 203 10.718 −4.635 76.792 1.00 46.99 ATOM 435 CD GLN 203 11.663 −5.579 76.093 1.00 48.26 ATOM 436 OE1 GLN 203 11.253 −6.602 75.541 1.00 47.41 ATOM 437 NE2 GLN 203 12.945 −5.236 76.109 1.00 49.20 ATOM 438 C GLN 203 9.526 −2.169 77.515 1.00 46.24 ATOM 439 O GLN 203 10.416 −1.575 78.126 1.00 46.33 ATOM 440 N ALA 204 8.395 −2.576 78.086 1.00 46.69 ATOM 441 CA ALA 204 8.169 −2.376 79.510 1.00 47.75 ATOM 442 CB ALA 204 6.754 −2.731 79.869 1.00 47.77 ATOM 443 C ALA 204 9.155 −3.326 80.193 1.00 49.20 ATOM 444 O ALA 204 9.282 −4.492 79.799 1.00 50.45 ATOM 445 N CYS 205 9.854 −2.830 81.209 1.00 49.03 ATOM 446 CA CYS 205 10.870 −3.618 81.895 1.00 47.82 ATOM 447 C CYS 205 10.596 −3.914 83.372 1.00 47.00 ATOM 448 O CYS 205 11.342 −3.464 84.244 1.00 47.48 ATOM 449 CB CYS 205 12.214 −2.899 81.749 1.00 49.40 ATOM 450 SG CYS 205 12.089 −1.097 82.038 1.00 52.40 ATOM 451 N PRO 206 9.535 −4.692 83.671 1.00 45.36 ATOM 452 CD PRO 206 8.592 −5.258 82.690 1.00 44.00 ATOM 453 CA PRO 206 9.142 −5.069 85.037 1.00 43.93 ATOM 454 CB PRO 206 8.083 −6.135 84.797 1.00 42.82 ATOM 455 CG PRO 206 7.423 −5.660 83.552 1.00 42.86 ATOM 456 C PRO 206 10.294 −5.603 85.890 1.00 43.70 ATOM 457 O PRO 206 11.013 −6.495 85.458 1.00 43.27 ATOM 458 N LYS 207 10.471 −5.059 87.094 1.00 44.28 ATOM 459 CA LYS 207 11.533 −5.521 87.992 1.00 45.36 ATOM 460 CB LYS 207 11.664 −4.626 89.235 1.00 43.66 ATOM 461 CG LYS 207 12.061 −3.179 89.019 1.00 42.40 ATOM 462 CD LYS 207 13.436 −3.046 88.429 1.00 41.07 ATOM 463 CE LYS 207 14.481 −3.725 89.264 1.00 40.58 ATOM 464 NZ LYS 207 15.758 −3.685 88.510 1.00 40.89 ATOM 465 C LYS 207 11.157 −6.913 88.481 1.00 47.60 ATOM 466 O LYS 207 10.126 −7.086 89.126 1.00 49.38 ATOM 467 N VAL 208 11.975 −7.910 88.185 1.00 49.19 ATOM 468 CA VAL 208 11.669 −9.248 88.654 1.00 50.40 ATOM 469 CB VAL 208 11.317 −10.192 87.512 1.00 49.17 ATOM 470 CG1 VAL 208 10.947 −11.548 88.072 1.00 48.47 ATOM 471 CG2 VAL 208 10.171 −9.621 86.720 1.00 49.94 ATOM 472 C VAL 208 12.867 −9.800 89.379 1.00 52.48 ATOM 473 O VAL 208 13.950 −9.895 88.820 1.00 53.30 ATOM 474 N SER 209 12.667 −10.153 90.638 1.00 55.82 ATOM 475 CA SER 209 13.744 −10.701 91.442 1.00 59.23 ATOM 476 CB SER 209 14.271 −9.657 92.433 1.00 60.00 ATOM 477 OG SER 209 13.294 −9.300 93.397 1.00 59.59 ATOM 478 C SER 209 13.251 −11.912 92.205 1.00 60.56 ATOM 479 O SER 209 12.328 −11.819 93.015 1.00 61.51 ATOM 480 N PHE 210 13.863 −13.054 91.927 1.00 61.88 ATOM 481 CA PHE 210 13.509 −14.293 92.596 1.00 62.55 ATOM 482 CB PHE 210 12.163 −14.831 92.088 1.00 62.36 ATOM 483 CG PHE 210 12.173 −15.247 90.645 1.00 62.80 ATOM 484 CD1 PHE 210 12.312 −14.303 89.634 1.00 63.22 ATOM 485 CD2 PHE 210 12.044 −16.588 90.295 1.00 63.02 ATOM 486 CE1 PHE 210 12.321 −14.690 88.294 1.00 62.99 ATOM 487 CE2 PHE 210 12.052 −16.980 88.957 1.00 63.02 ATOM 488 CZ PHE 210 12.191 −16.027 87.956 1.00 62.16 ATOM 489 C PHE 210 14.624 −15.285 92.317 1.00 62.59 ATOM 490 O PHE 210 15.231 −15.266 91.245 1.00 62.81 ATOM 491 N GLU 211 14.908 −16.138 93.291 1.00 62.66 ATOM 492 CA GLU 211 15.963 −17.120 93.127 1.00 62.85 ATOM 493 CB GLU 211 16.274 −17.768 94.490 1.00 63.27 ATOM 494 CG GLU 211 17.354 −16.985 95.278 1.00 65.06 ATOM 495 CD GLU 211 17.291 −17.160 96.800 1.00 65.99 ATOM 496 OE1 GLU 211 17.055 −18.299 97.267 1.00 66.91 ATOM 497 OE2 GLU 211 17.497 −16.153 97.528 1.00 63.93 ATOM 498 C GLU 211 15.645 −18.161 92.036 1.00 61.85 ATOM 499 O GLU 211 14.538 −18.703 91.965 1.00 61.07 ATOM 500 N PRO 212 16.617 −18.406 91.136 1.00 60.73 ATOM 501 CD PRO 212 17.853 −17.606 91.033 1.00 60.13 ATOM 502 CA PRO 212 16.529 −19.355 90.019 1.00 60.07 ATOM 503 CB PRO 212 17.865 −19.151 89.295 1.00 60.56 ATOM 504 CG PRO 212 18.190 −17.724 89.579 1.00 58.99 ATOM 505 C PRO 212 16.318 −20.824 90.424 1.00 59.13 ATOM 506 O PRO 212 17.062 −21.371 91.241 1.00 58.14 ATOM 507 N ILE 213 15.308 −21.454 89.834 1.00 58.39 ATOM 508 CA ILE 213 14.999 −22.851 90.111 1.00 57.51 ATOM 509 CB ILE 213 13.582 −23.226 89.634 1.00 57.45 ATOM 510 CG2 ILE 213 12.936 −24.123 90.645 1.00 58.00 ATOM 511 CG1 ILE 213 12.716 −21.978 89.461 1.00 58.13 ATOM 512 CD1 ILE 213 12.426 −21.230 90.750 1.00 58.27 ATOM 513 C ILE 213 15.995 −23.705 89.330 1.00 57.45 ATOM 514 O ILE 213 16.398 −23.335 88.225 1.00 57.51 ATOM 515 N PRO 214 16.406 −24.863 89.888 1.00 56.69 ATOM 516 CD PRO 214 16.153 −25.380 91.240 1.00 55.47 ATOM 517 CA PRO 214 17.361 −25.729 89.193 1.00 55.78 ATOM 518 CB PRO 214 17.614 −26.845 90.197 1.00 54.06 ATOM 519 CG PRO 214 17.405 −26.184 91.489 1.00 54.24 ATOM 520 C PRO 214 16.789 −26.257 87.894 1.00 56.50 ATOM 521 O PRO 214 15.620 −26.637 87.820 1.00 55.06 ATOM 522 N ILE 215 17.640 −26.271 86.878 1.00 58.07 ATOM 523 CA ILE 215 17.286 −26.745 85.555 1.00 58.99 ATOM 524 CB ILE 215 17.892 −25.815 84.461 1.00 60.28 ATOM 525 CG2 ILE 215 17.752 −26.442 83.088 1.00 61.12 ATOM 526 CG1 ILE 215 17.218 −24.435 84.499 1.00 61.06 ATOM 527 CD1 ILE 215 15.713 −24.448 84.230 1.00 60.70 ATOM 528 C ILE 215 17.846 −28.153 85.391 1.00 59.41 ATOM 529 O ILE 215 18.987 −28.418 85.754 1.00 58.13 ATOM 530 N HIS 216 17.019 −29.051 84.866 1.00 61.77 ATOM 531 CA HIS 216 17.403 −30.436 84.617 1.00 63.93 ATOM 532 CB HIS 216 16.393 −31.403 85.235 1.00 64.72 ATOM 533 CG HIS 216 16.375 −31.414 86.730 1.00 67.28 ATOM 534 CD2 HIS 216 15.441 −30.977 87.609 1.00 67.94 ATOM 535 ND1 HIS 216 17.375 −31.987 87.483 1.00 68.72 ATOM 536 CE1 HIS 216 17.057 −31.908 88.766 1.00 68.43 ATOM 537 NE2 HIS 216 15.890 −31.300 88.868 1.00 69.02 ATOM 538 C HIS 216 17.378 −30.655 83.105 1.00 65.39 ATOM 539 O HIS 216 16.331 −30.504 82.474 1.00 65.51 ATOM 540 N TYR 217 18.517 −31.002 82.517 1.00 66.95 ATOM 541 CA TYR 217 18.562 −31.260 81.081 1.00 67.77 ATOM 542 CB TYR 217 19.964 −30.971 80.530 1.00 69.80 ATOM 543 CG TYR 217 20.183 −31.360 79.076 1.00 72.85 ATOM 544 CD1 TYR 217 20.066 −32.688 78.656 1.00 73.62 ATOM 545 CE1 TYR 217 20.306 −33.062 77.332 1.00 73.91 ATOM 546 CD2 TYR 217 20.543 −30.408 78.124 1.00 74.21 ATOM 547 CE2 TYR 217 20.787 −30.774 76.791 1.00 75.39 ATOM 548 CZ TYR 217 20.664 −32.105 76.407 1.00 75.03 ATOM 549 OH TYR 217 20.905 −32.476 75.101 1.00 75.25 ATOM 550 C TYR 217 18.198 −32.726 80.881 1.00 67.53 ATOM 551 O TYR 217 18.779 −33.611 81.512 1.00 66.37 ATOM 552 N CYS 218 17.220 −32.977 80.021 1.00 68.26 ATOM 553 CA CYS 218 16.801 −34.345 79.736 1.00 69.95 ATOM 554 C CYS 218 17.146 −34.676 78.291 1.00 70.18 ATOM 555 O CYS 218 17.368 −33.768 77.483 1.00 71.00 ATOM 556 CB CYS 218 15.299 −34.515 79.952 1.00 70.79 ATOM 557 SG CYS 218 14.717 −34.185 81.647 1.00 73.86 ATOM 558 N ALA 219 17.190 −35.969 77.972 1.00 69.23 ATOM 559 CA ALA 219 17.525 −36.418 76.622 1.00 67.68 ATOM 560 CB ALA 219 17.950 −37.874 76.651 1.00 68.44 ATOM 561 C ALA 219 16.367 −36.224 75.644 1.00 66.31 ATOM 562 O ALA 219 15.224 −36.577 75.937 1.00 64.91 ATOM 563 N PRO 220 16.657 −35.652 74.462 1.00 65.58 ATOM 564 CD PRO 220 17.955 −35.074 74.079 1.00 65.63 ATOM 565 CA PRO 220 15.657 −35.394 73.420 1.00 64.40 ATOM 566 CB PRO 220 16.352 −34.386 72.500 1.00 64.51 ATOM 567 CG PRO 220 17.515 −33.858 73.317 1.00 65.89 ATOM 568 C PRO 220 15.298 −36.670 72.676 1.00 63.38 ATOM 569 O PRO 220 16.095 −37.609 72.625 1.00 63.61 ATOM 570 N ALA 221 14.104 −36.691 72.090 1.00 61.61 ATOM 571 CA ALA 221 13.645 −37.852 71.345 1.00 59.16 ATOM 572 CB ALA 221 12.397 −37.503 70.558 1.00 57.25 ATOM 573 C ALA 221 14.751 −38.323 70.407 1.00 58.51 ATOM 574 O ALA 221 15.303 −37.532 69.645 1.00 58.11 ATOM 575 N GLY 222 15.092 −39.608 70.492 1.00 58.44 ATOM 576 CA GLY 222 16.121 −40.163 69.632 1.00 58.13 ATOM 577 C GLY 222 17.508 −40.316 70.229 1.00 58.27 ATOM 578 O GLY 222 18.405 −40.830 69.560 1.00 57.97 ATOM 579 N PHE 223 17.700 −39.888 71.475 1.00 58.69 ATOM 580 CA PHE 223 19.020 −39.989 72.102 1.00 58.31 ATOM 581 CB PHE 223 19.711 −38.625 72.073 1.00 59.64 ATOM 582 CG PHE 223 20.030 −38.136 70.690 1.00 60.13 ATOM 583 CD1 PHE 223 19.032 −37.613 69.873 1.00 59.78 ATOM 584 CD2 PHE 223 21.330 −38.222 70.197 1.00 59.77 ATOM 585 CE1 PHE 223 19.323 −37.182 68.588 1.00 60.31 ATOM 586 CE2 PHE 223 21.632 −37.797 68.919 1.00 60.24 ATOM 587 CZ PHE 223 20.626 −37.273 68.107 1.00 61.40 ATOM 588 C PHE 223 19.052 −40.530 73.527 1.00 57.51 ATOM 589 O PHE 223 18.016 −40.708 74.165 1.00 56.31 ATOM 590 N ALA 224 20.261 −40.787 74.021 1.00 57.34 ATOM 591 CA ALA 224 20.447 −41.309 75.373 1.00 58.31 ATOM 592 CB ALA 224 20.842 −42.773 75.311 1.00 58.16 ATOM 593 C ALA 224 21.517 −40.514 76.116 1.00 58.54 ATOM 594 O ALA 224 22.404 −39.945 75.491 1.00 59.61 ATOM 595 N ILE 225 21.436 −40.486 77.444 1.00 57.96 ATOM 596 CA ILE 225 22.401 −39.751 78.255 1.00 57.94 ATOM 597 CB ILE 225 21.699 −38.763 79.225 1.00 58.15 ATOM 598 CG2 ILE 225 22.734 −38.081 80.114 1.00 58.23 ATOM 599 CG1 ILE 225 20.904 −37.712 78.444 1.00 58.02 ATOM 600 CD1 ILE 225 20.136 −36.737 79.329 1.00 55.55 ATOM 601 C ILE 225 23.278 −40.666 79.101 1.00 58.42 ATOM 602 O ILE 225 22.794 −41.341 80.006 1.00 59.16 ATOM 603 N LEU 226 24.572 −40.686 78.815 1.00 58.75 ATOM 604 CA LEU 226 25.484 −41.509 79.597 1.00 59.39 ATOM 605 CB LEU 226 26.569 −42.109 78.699 1.00 57.81 ATOM 606 CG LEU 226 26.083 −42.866 77.461 1.00 56.08 ATOM 607 CD1 LEU 226 27.257 −43.550 76.802 1.00 55.05 ATOM 608 CD2 LEU 226 25.039 −43.886 77.838 1.00 55.26 ATOM 609 C LEU 226 26.101 −40.612 80.667 1.00 60.63 ATOM 610 O LEU 226 26.257 −39.412 80.453 1.00 60.94 ATOM 611 N LYS 227 26.448 −41.197 81.810 1.00 62.31 ATOM 612 CA LYS 227 27.022 −40.452 82.930 1.00 63.91 ATOM 613 CB LYS 227 25.940 −40.230 84.000 1.00 63.10 ATOM 614 CG LYS 227 26.440 −39.783 85.373 1.00 62.19 ATOM 615 CD LYS 227 25.292 −39.708 86.391 1.00 61.38 ATOM 616 CE LYS 227 25.767 −39.220 87.765 1.00 61.56 ATOM 617 NZ LYS 227 24.653 −39.044 88.746 1.00 59.42 ATOM 618 C LYS 227 28.208 −41.169 83.560 1.00 65.80 ATOM 619 O LYS 227 28.038 −42.199 84.205 1.00 67.24 ATOM 620 N CYS 228 29.409 −40.631 83.387 1.00 68.12 ATOM 621 CA CYS 228 30.578 −41.262 83.983 1.00 70.64 ATOM 622 C CYS 228 30.444 −41.156 85.496 1.00 70.41 ATOM 623 O CYS 228 30.085 −40.107 86.019 1.00 70.19 ATOM 624 CB CYS 228 31.871 −40.590 83.511 1.00 73.46 ATOM 625 SG CYS 228 33.366 −41.502 84.026 1.00 78.70 ATOM 626 N ASN 229 30.733 −42.243 86.200 1.00 71.33 ATOM 627 CA ASN 229 30.600 −42.255 87.647 1.00 71.92 ATOM 628 CB ASN 229 29.857 −43.508 88.082 1.00 72.45 ATOM 629 CG ASN 229 28.411 −43.492 87.652 1.00 73.11 ATOM 630 OD1 ASN 229 27.647 −42.610 88.051 1.00 72.87 ATOM 631 ND2 ASN 229 28.022 −44.465 86.830 1.00 72.92 ATOM 632 C ASN 229 31.867 −42.109 88.469 1.00 72.51 ATOM 633 O ASN 229 31.785 −42.025 89.688 1.00 72.22 ATOM 634 N ASN 230 33.033 −42.089 87.829 1.00 74.40 ATOM 635 CA ASN 230 34.272 −41.910 88.582 1.00 76.62 ATOM 636 CB ASN 230 35.455 −41.654 87.648 1.00 77.04 ATOM 637 CG ASN 230 35.879 −42.887 86.894 1.00 78.06 ATOM 638 OD1 ASN 230 36.745 −42.818 86.020 1.00 78.68 ATOM 639 ND2 ASN 230 35.278 −44.024 87.232 1.00 78.86 ATOM 640 C ASN 230 34.064 −40.685 89.458 1.00 77.81 ATOM 641 O ASN 230 33.496 −39.687 89.010 1.00 78.44 ATOM 642 N LYS 231 34.507 −40.754 90.706 1.00 79.00 ATOM 643 CA LYS 231 34.338 −39.623 91.608 1.00 80.19 ATOM 644 CB LYS 231 34.648 −40.048 93.049 1.00 81.06 ATOM 645 CG LYS 231 33.678 −41.098 93.576 1.00 81.81 ATOM 646 CD LYS 231 34.028 −41.600 94.968 1.00 82.80 ATOM 647 CE LYS 231 33.081 −42.740 95.376 1.00 83.45 ATOM 648 NZ LYS 231 33.385 −43.321 96.720 1.00 82.56 ATOM 649 C LYS 231 35.235 −38.474 91.169 1.00 80.35 ATOM 650 O LYS 231 35.008 −37.321 91.536 1.00 80.46 ATOM 651 N THR 232 36.245 −38.803 90.368 1.00 80.83 ATOM 652 CA THR 232 37.188 −37.817 89.843 1.00 81.48 ATOM 653 CB THR 232 38.552 −37.900 90.545 1.00 81.81 ATOM 654 OG1 THR 232 38.381 −37.665 91.947 1.00 82.72 ATOM 655 CG2 THR 232 39.515 −36.865 89.965 1.00 81.15 ATOM 656 C THR 232 37.399 −38.103 88.367 1.00 81.71 ATOM 657 O THR 232 38.174 −38.987 87.998 1.00 82.58 ATOM 658 N PHE 233 36.706 −37.350 87.526 1.00 81.77 ATOM 659 CA PHE 233 36.807 −37.537 86.089 1.00 81.98 ATOM 660 CB PHE 233 35.426 −37.881 85.532 1.00 80.95 ATOM 661 CG PHE 233 35.448 −38.347 84.117 1.00 80.20 ATOM 662 CD1 PHE 233 36.242 −39.423 83.746 1.00 79.86 ATOM 663 CD2 PHE 233 34.675 −37.713 83.153 1.00 80.45 ATOM 664 CE1 PHE 233 36.269 −39.865 82.434 1.00 80.01 ATOM 665 CE2 PHE 233 34.692 −38.145 81.840 1.00 80.85 ATOM 666 CZ PHE 233 35.493 −39.226 81.477 1.00 80.97 ATOM 667 C PHE 233 37.351 −36.276 85.428 1.00 82.46 ATOM 668 O PHE 233 36.918 −35.172 85.749 1.00 82.61 ATOM 669 N ASN 234 38.304 −36.432 84.513 1.00 83.24 ATOM 670 CA ASN 234 38.874 −35.271 83.841 1.00 84.16 ATOM 671 CB ASN 234 40.354 −35.499 83.532 1.00 86.83 ATOM 672 CG ASN 234 40.574 −36.548 82.469 1.00 90.05 ATOM 673 OD1 ASN 234 39.934 −36.527 81.421 1.00 91.19 ATOM 674 ND2 ASN 234 41.507 −37.457 82.725 1.00 92.74 ATOM 675 C ASN 234 38.117 −34.914 82.559 1.00 83.56 ATOM 676 O ASN 234 38.633 −34.196 81.697 1.00 83.14 ATOM 677 N GLY 235 36.897 −35.433 82.444 1.00 82.91 ATOM 678 CA GLY 235 36.049 −35.147 81.300 1.00 81.77 ATOM 679 C GLY 235 36.479 −35.646 79.936 1.00 80.76 ATOM 680 O GLY 235 35.687 −35.623 78.996 1.00 80.76 ATOM 681 N THR 236 37.722 −36.095 79.808 1.00 79.92 ATOM 682 CA THR 236 38.203 −36.583 78.521 1.00 78.75 ATOM 683 CB THR 236 39.368 −35.722 77.992 1.00 79.46 ATOM 684 OG1 THR 236 39.526 −35.948 76.586 1.00 79.72 ATOM 685 CG2 THR 236 40.671 −36.091 78.698 1.00 79.62 ATOM 686 C THR 236 38.676 −38.020 78.618 1.00 77.39 ATOM 687 O THR 236 38.821 −38.564 79.706 1.00 77.35 ATOM 688 N GLY 237 38.926 −38.628 77.469 1.00 76.80 ATOM 689 CA GLY 237 39.390 −39.998 77.455 1.00 76.72 ATOM 690 C GLY 237 38.283 −40.994 77.729 1.00 76.45 ATOM 691 O GLY 237 37.106 −40.659 77.589 1.00 76.57 ATOM 692 N PRO 238 38.634 −42.235 78.113 1.00 75.99 ATOM 693 CD PRO 238 40.000 −42.777 78.002 1.00 75.67 ATOM 694 CA PRO 238 37.689 −43.311 78.413 1.00 75.71 ATOM 695 CB PRO 238 38.456 −44.544 77.980 1.00 75.43 ATOM 696 CG PRO 238 39.824 −44.215 78.454 1.00 75.46 ATOM 697 C PRO 238 37.247 −43.404 79.876 1.00 75.60 ATOM 698 O PRO 238 38.014 −43.116 80.795 1.00 74.29 ATOM 699 N CYS 239 35.996 −43.811 80.065 1.00 76.23 ATOM 700 CA CYS 239 35.401 −43.978 81.386 1.00 77.64 ATOM 701 C CYS 239 35.078 −45.462 81.561 1.00 77.75 ATOM 702 O CYS 239 34.724 −46.151 80.602 1.00 77.99 ATOM 703 CB CYS 239 34.114 −43.136 81.511 1.00 78.55 ATOM 704 SG CYS 239 33.201 −43.307 83.092 1.00 79.98 ATOM 705 N THR 240 35.205 −45.950 82.789 1.00 77.99 ATOM 706 CA THR 240 34.936 −47.352 83.086 1.00 77.29 ATOM 707 CB THR 240 36.156 −47.984 83.808 1.00 77.48 ATOM 708 OG1 THR 240 36.642 −47.088 84.817 1.00 77.79 ATOM 709 CG2 THR 240 37.276 −48.253 82.812 1.00 76.21 ATOM 710 C THR 240 33.651 −47.555 83.914 1.00 76.52 ATOM 711 O THR 240 32.878 −48.482 83.653 1.00 76.31 ATOM 712 N ASN 241 33.427 −46.683 84.898 1.00 74.90 ATOM 713 CA ASN 241 32.239 −46.740 85.760 1.00 72.80 ATOM 714 CB ASN 241 32.617 −46.258 87.171 1.00 72.80 ATOM 715 CG ASN 241 31.621 −46.691 88.241 1.00 72.83 ATOM 716 OD1 ASN 241 30.404 −46.657 88.031 1.00 73.02 ATOM 717 ND2 ASN 241 32.142 −47.079 89.402 1.00 71.56 ATOM 718 C ASN 241 31.195 −45.797 85.132 1.00 71.45 ATOM 719 O ASN 241 31.185 −44.601 85.419 1.00 70.59 ATOM 720 N VAL 242 30.323 −46.333 84.278 1.00 69.95 ATOM 721 CA VAL 242 29.319 −45.512 83.591 1.00 68.27 ATOM 722 CB VAL 242 29.779 −45.171 82.153 1.00 68.44 ATOM 723 CG1 VAL 242 30.532 −46.343 81.548 1.00 68.10 ATOM 724 CG2 VAL 242 28.574 −44.842 81.286 1.00 68.72 ATOM 725 C VAL 242 27.911 −46.091 83.494 1.00 66.92 ATOM 726 O VAL 242 27.736 −47.279 83.258 1.00 67.05 ATOM 727 N SER 243 26.908 −45.231 83.650 1.00 65.86 ATOM 728 CA SER 243 25.513 −45.657 83.568 1.00 65.72 ATOM 729 CB SER 243 24.911 −45.773 84.975 1.00 64.61 ATOM 730 OG SER 243 25.167 −44.631 85.765 1.00 62.69 ATOM 731 C SER 243 24.655 −44.729 82.700 1.00 65.75 ATOM 732 O SER 243 25.138 −43.719 82.195 1.00 66.44 ATOM 733 N THR 244 23.386 −45.089 82.523 1.00 65.22 ATOM 734 CA THR 244 22.440 −44.307 81.722 1.00 64.94 ATOM 735 CB THR 244 21.692 −45.202 80.714 1.00 65.14 ATOM 736 OG1 THR 244 22.448 −45.286 79.501 1.00 65.13 ATOM 737 CG2 THR 244 20.294 −44.655 80.422 1.00 64.17 ATOM 738 C THR 244 21.408 −43.644 82.614 1.00 65.03 ATOM 739 O THR 244 20.913 −44.262 83.550 1.00 66.14 ATOM 740 N VAL 245 21.065 −42.397 82.310 1.00 64.75 ATOM 741 CA VAL 245 20.089 −41.669 83.112 1.00 64.42 ATOM 742 CB VAL 245 20.777 −40.574 83.939 1.00 64.72 ATOM 743 CG1 VAL 245 21.922 −41.172 84.732 1.00 64.56 ATOM 744 CG2 VAL 245 21.291 −39.477 83.019 1.00 65.00 ATOM 745 C VAL 245 19.008 −41.016 82.264 1.00 64.37 ATOM 746 O VAL 245 19.148 −40.887 81.052 1.00 62.59 ATOM 747 N GLN 246 17.927 −40.600 82.910 1.00 65.67 ATOM 748 CA GLN 246 16.839 −39.947 62.195 1.00 67.31 ATOM 749 CB GLN 246 15.528 −40.083 82.972 1.00 69.55 ATOM 750 CG GLN 246 15.009 −41.514 83.055 1.00 72.91 ATOM 751 CD GLN 246 14.973 −42.189 81.691 1.00 74.79 ATOM 752 OE1 GLN 246 14.414 −41.645 80.737 1.00 76.33 ATOM 753 NE2 GLN 246 15.568 −43.381 81.593 1.00 74.80 ATOM 754 C GLN 246 17.174 −38.477 81.991 1.00 67.14 ATOM 755 O GLN 246 17.049 −37.952 80.887 1.00 67.40 ATOM 756 N CYS 247 17.603 −37.819 83.064 1.00 67.11 ATOM 757 CA CYS 247 17.981 −36.408 83.009 1.00 66.41 ATOM 758 C CYS 247 19.173 −36.223 83.942 1.00 64.14 ATOM 759 O CYS 247 19.394 −37.048 84.834 1.00 63.44 ATOM 760 CB CYS 247 16.821 −35.516 83.465 1.00 68.57 ATOM 761 SG CYS 247 15.192 −35.863 82.704 1.00 72.95 ATOM 762 N THR 248 19.943 −35.155 83.736 1.00 61.65 ATOM 763 CA THR 248 21.115 −34.882 84.571 1.00 58.60 ATOM 764 CB THR 248 22.015 −33.789 83.953 1.00 58.51 ATOM 765 OG1 THR 248 21.401 −32.506 84.118 1.00 58.42 ATOM 766 CG2 THR 248 22.224 −34.048 82.472 1.00 57.39 ATOM 767 C THR 248 20.649 −34.404 85.938 1.00 56.78 ATOM 768 O THR 248 19.460 −34.479 86.248 1.00 56.77 ATOM 769 N HIS 249 21.575 −33.914 86.759 1.00 54.48 ATOM 770 CA HIS 249 21.204 −33.423 88.085 1.00 52.32 ATOM 771 CB HIS 249 22.408 −33.455 89.036 1.00 50.67 ATOM 772 CG HIS 249 23.557 −32.617 88.581 1.00 50.88 ATOM 773 CD2 HIS 249 23.960 −31.378 88.951 1.00 51.06 ATOM 774 ND1 HIS 249 24.418 −33.016 87.582 1.00 52.07 ATOM 775 CE1 HIS 249 25.300 −32.059 87.354 1.00 52.55 ATOM 776 NE2 HIS 249 25.043 −31.053 88.171 1.00 51.62 ATOM 777 C HIS 249 20.648 −31.997 88.000 1.00 51.12 ATOM 778 O HIS 249 20.672 −31.366 86.943 1.00 50.41 ATOM 779 N GLY 250 20.120 −31.504 89.112 1.00 50.12 ATOM 780 CA GLY 250 19.589 −30.158 89.128 1.00 48.39 ATOM 781 C GLY 250 20.738 −29.188 89.013 1.00 47.71 ATOM 782 O GLY 250 21.720 −29.274 89.754 1.00 47.82 ATOM 783 N ILE 251 20.631 −28.262 88.075 1.00 47.08 ATOM 784 CA ILE 251 21.692 −27.295 87.898 1.00 47.14 ATOM 785 CB ILE 251 22.386 −27.494 86.533 1.00 46.53 ATOM 786 CG2 ILE 251 23.380 −26.363 86.268 1.00 46.08 ATOM 787 CG1 ILE 251 23.100 −28.845 86.534 1.00 46.01 ATOM 788 CD1 ILE 251 23.697 −29.231 85.209 1.00 46.76 ATOM 789 C ILE 251 21.222 −25.856 88.050 1.00 47.08 ATOM 790 O ILE 251 20.219 −25.439 87.479 1.00 46.45 ATOM 791 N ARG 252 21.953 −25.114 88.868 1.00 47.74 ATOM 792 CA ARG 252 21.651 −23.722 89.101 1.00 48.23 ATOM 793 CB ARG 252 22.398 −23.209 90.335 1.00 49.56 ATOM 794 CG ARG 252 21.642 −23.363 91.631 1.00 52.05 ATOM 795 CD ARG 252 21.428 −24.816 91.987 1.00 55.46 ATOM 796 NE ARG 252 20.534 −24.934 93.127 1.00 58.57 ATOM 797 CZ ARG 252 20.800 −24.438 94.330 1.00 61.06 ATOM 798 NH1 ARG 252 21.942 −23.796 94.547 1.00 61.62 ATOM 799 NH2 ARG 252 19.917 −24.568 95.313 1.00 62.98 ATOM 800 C ARG 252 22.125 −22.965 87.877 1.00 47.35 ATOM 801 O ARG 252 23.322 −22.949 87.577 1.00 48.58 ATOM 802 N PRO 253 21.194 −22.354 87.134 1.00 45.23 ATOM 803 CD PRO 253 19.728 −22.423 87.233 1.00 44.55 ATOM 804 CA PRO 253 21.595 −21.604 85.949 1.00 43.24 ATOM 805 CB PRO 253 20.288 −21.483 85.179 1.00 42.38 ATOM 806 CG PRO 253 19.293 −21.350 86.272 1.00 43.19 ATOM 807 C PRO 253 22.182 −20.256 86.375 1.00 41.47 ATOM 808 O PRO 253 21.744 −19.199 85.926 1.00 42.48 ATOM 809 N VAL 254 23.179 −20.305 87.255 1.00 39.38 ATOM 810 CA VAL 254 23.822 −19.092 87.751 1.00 37.91 ATOM 811 CB VAL 254 24.819 −19.384 88.879 1.00 37.89 ATOM 812 CG1 VAL 254 25.491 −18.100 89.330 1.00 36.95 ATOM 813 CG2 VAL 254 24.107 −20.023 90.030 1.00 40.36 ATOM 814 C VAL 254 24.589 −18.384 86.661 1.00 36.14 ATOM 815 O VAL 254 25.346 −19.000 85.913 1.00 37.64 ATOM 816 N VAL 255 24.399 −17.078 86.588 1.00 32.62 ATOM 817 CA VAL 255 25.090 −16.278 85.607 1.00 30.04 ATOM 818 CB VAL 255 24.103 −15.366 84.867 1.00 31.25 ATOM 819 CG1 VAL 255 24.783 −14.073 84.437 1.00 31.11 ATOM 820 CG2 VAL 255 23.571 −16.105 83.654 1.00 32.07 ATOM 821 C VAL 255 26.165 −15.463 86.298 1.00 26.49 ATOM 822 O VAL 255 25.878 −14.632 87.144 1.00 24.49 ATOM 823 N SER 256 27.412 −15.706 85.931 1.00 24.46 ATOM 824 CA SER 256 28.486 −14.982 86.556 1.00 23.46 ATOM 825 CB SER 256 28.585 −15.389 88.010 1.00 22.73 ATOM 826 OG SER 256 29.018 −16.727 88.096 1.00 21.19 ATOM 827 C SER 256 29.846 −15.182 85.915 1.00 23.86 ATOM 828 O SER 256 30.047 −16.034 85.038 1.00 22.73 ATOM 829 N SER 257 30.787 −14.384 86.401 1.00 23.62 ATOM 830 CA SER 257 32.159 −14.423 85.941 1.00 23.31 ATOM 831 CB SER 257 32.559 −13.053 85.417 1.00 22.82 ATOM 832 OG SER 257 32.592 −12.107 86.466 1.00 20.86 ATOM 833 C SER 257 33.063 −14.804 87.106 1.00 23.53 ATOM 834 O SER 257 32.629 −14.829 88.250 1.00 23.12 ATOM 835 N GLN 258 34.313 −15.119 86.792 1.00 24.34 ATOM 836 CA GLN 258 35.327 −15.475 87.785 1.00 26.23 ATOM 837 CB GLN 258 35.699 −14.223 88.565 1.00 25.47 ATOM 838 CG GLN 258 35.659 −13.014 87.684 1.00 25.81 ATOM 839 CD GLN 258 36.430 −11.876 88.256 1.00 26.39 ATOM 840 OE1 GLN 258 36.368 −11.623 89.454 1.00 27.90 ATOM 841 NE2 GLN 258 37.163 −11.168 87.407 1.00 23.70 ATOM 842 C GLN 258 34.995 −16.601 88.757 1.00 26.10 ATOM 843 O GLN 258 35.661 −17.630 88.785 1.00 27.43 ATOM 844 N LEU 259 33.965 −16.397 89.559 1.00 26.43 ATOM 845 CA LEU 259 33.563 −17.382 90.538 1.00 25.71 ATOM 846 CB LEU 259 33.304 −16.692 91.865 1.00 25.10 ATOM 847 CG LEU 259 34.388 −15.692 92.261 1.00 24.45 ATOM 848 CD1 LEU 259 33.952 −14.868 93.466 1.00 20.24 ATOM 849 CD2 LEU 259 35.672 −16.457 92.530 1.00 26.19 ATOM 850 C LEU 259 32.295 −18.068 90.083 1.00 26.56 ATOM 851 O LEU 259 31.402 −17.423 89.533 1.00 27.02 ATOM 852 N LEU 260 32.236 −19.377 90.310 1.00 26.59 ATOM 853 CA LEU 260 31.076 −20.199 89.977 1.00 25.55 ATOM 854 CB LEU 260 31.528 −21.570 89.490 1.00 21.73 ATOM 855 CG LEU 260 32.353 −21.522 88.222 1.00 20.50 ATOM 856 CD1 LEU 260 32.904 −22.888 87.902 1.00 21.75 ATOM 857 CD2 LEU 260 31.485 −21.036 87.102 1.00 19.68 ATOM 858 C LEU 260 30.306 −20.347 91.282 1.00 26.59 ATOM 859 O LEU 260 30.823 −20.923 92.233 1.00 28.36 ATOM 860 N LEU 261 29.076 −19.847 91.330 1.00 27.70 ATOM 861 CA LEU 261 28.283 −19.905 92.557 1.00 28.07 ATOM 862 CB LEU 261 27.611 −18.555 92.769 1.00 28.66 ATOM 863 CG LEU 261 28.555 −17.374 92.533 1.00 28.66 ATOM 864 CD1 LEU 261 27.784 −16.071 92.672 1.00 28.33 ATOM 865 CD2 LEU 261 29.722 −17.433 93.517 1.00 28.00 ATOM 866 C LEU 261 27.233 −21.004 92.632 1.00 28.30 ATOM 867 O LEU 261 26.633 −21.362 91.635 1.00 27.56 ATOM 868 N ASN 262 27.022 −21.538 93.831 1.00 30.19 ATOM 869 CA ASN 262 26.026 −22.589 94.062 1.00 30.65 ATOM 870 CB ASN 262 24.627 −21.988 93.972 1.00 30.68 ATOM 871 CG ASN 262 24.446 −20.825 94.915 1.00 32.60 ATOM 872 OD1 ASN 262 25.131 −20.716 95.937 1.00 32.65 ATOM 873 ND2 ASN 262 23.506 −19.952 94.590 1.00 33.30 ATOM 874 C ASN 262 26.107 −23.820 93.158 1.00 29.62 ATOM 875 O ASN 262 25.084 −24.400 92.777 1.00 27.50 ATOM 876 N GLY 263 27.328 −24.226 92.835 1.00 29.42 ATOM 877 CA GLY 263 27.501 −25.384 91.983 1.00 30.33 ATOM 878 C GLY 263 27.889 −26.635 92.734 1.00 29.97 ATOM 879 O GLY 263 27.951 −26.638 93.954 1.00 30.00 ATOM 880 N SER 264 28.148 −27.704 91.991 1.00 31.78 ATOM 881 CA SER 264 28.540 −28.977 92.579 1.00 32.91 ATOM 882 CB SER 264 28.367 −30.119 91.576 1.00 32.66 ATOM 883 OG SER 264 27.014 −30.289 91.197 1.00 33.12 ATOM 884 C SER 264 29.992 −28.926 92.992 1.00 33.65 ATOM 885 O SER 264 30.813 −28.339 92.288 1.00 34.68 ATOM 886 N LEU 265 30.301 −29.537 94.133 1.00 34.04 ATOM 887 CA LEU 265 31.667 −29.588 94.627 1.00 34.32 ATOM 888 CB LEU 265 31.689 −29.585 96.155 1.00 32.99 ATOM 889 CG LEU 265 31.346 −28.271 96.859 1.00 33.66 ATOM 890 CD1 LEU 265 31.307 −28.477 98.352 1.00 34.03 ATOM 891 CD2 LEU 265 32.379 −27.219 96.520 1.00 34.44 ATOM 892 C LEU 265 32.297 −30.869 94.098 1.00 35.56 ATOM 893 O LEU 265 31.596 −31.751 93.607 1.00 34.43 ATOM 894 N ALA 266 33.622 −30.951 94.176 1.00 38.30 ATOM 895 CA ALA 266 34.352 −32.128 93.725 1.00 40.59 ATOM 896 CB ALA 266 35.769 −31.751 93.302 1.00 38.89 ATOM 897 C ALA 266 34.372 −33.070 94.920 1.00 43.62 ATOM 898 O ALA 266 34.755 −32.677 96.026 1.00 44.02 ATOM 899 N GLU 267 33.961 −34.314 94.691 1.00 46.39 ATOM 900 CA GLU 267 33.868 −35.303 95.754 1.00 49.11 ATOM 901 CB GLU 267 33.263 −36.593 95.198 1.00 51.72 ATOM 902 CG GLU 267 32.103 −36.352 94.222 1.00 56.02 ATOM 903 CD GLU 267 31.126 −37.527 94.130 1.00 57.75 ATOM 904 OE1 GLU 267 30.292 −37.680 95.053 1.00 58.56 ATOM 905 OE2 GLU 267 31.190 −38.294 93.139 1.00 58.03 ATOM 906 C GLU 267 35.125 −35.625 96.554 1.00 49.70 ATOM 907 O GLU 267 35.031 −35.933 97.736 1.00 50.00 ATOM 908 N GLU 268 36.299 −35.552 95.944 1.00 51.35 ATOM 909 CA GLU 268 37.510 −35.879 96.691 1.00 53.41 ATOM 910 CB GLU 268 38.332 −36.923 95.940 1.00 55.13 ATOM 911 CG GLU 268 37.589 −38.222 95.692 1.00 59.90 ATOM 912 CD GLU 268 38.264 −39.115 94.650 1.00 61.80 ATOM 913 OE1 GLU 268 37.689 −40.179 94.332 1.00 62.83 ATOM 914 OE2 GLU 268 39.358 −38.756 94.154 1.00 62.29 ATOM 915 C GLU 268 38.381 −34.672 96.964 1.00 53.78 ATOM 916 O GLU 268 38.293 −34.046 98.023 1.00 54.54 ATOM 917 N GLU 269 39.232 −34.355 96.000 1.00 53.53 ATOM 918 CA GLU 269 40.139 −33.231 96.132 1.00 53.58 ATOM 919 CB GLU 269 41.564 −33.689 95.841 1.00 55.20 ATOM 920 CG GLU 269 41.923 −35.009 96.487 1.00 57.76 ATOM 921 CD GLU 269 43.335 −35.450 96.151 1.00 59.84 ATOM 922 OE1 GLU 269 43.678 −36.621 96.416 1.00 59.87 ATOM 923 OE2 GLU 269 44.109 −34.623 95.626 1.00 62.07 ATOM 924 C GLU 269 39.746 −32.126 95.162 1.00 52.41 ATOM 925 O GLU 269 38.749 −32.252 94.452 1.00 53.19 ATOM 926 N VAL 270 40.530 −31.049 95.138 1.00 50.34 ATOM 927 CA VAL 270 40.269 −29.926 94.241 1.00 48.54 ATOM 928 CB VAL 270 41.091 −28.663 94.633 1.00 47.63 ATOM 929 CG1 VAL 270 41.172 −27.707 93.467 1.00 45.74 ATOM 930 CG2 VAL 270 40.424 −27.950 95.806 1.00 47.67 ATOM 931 C VAL 270 40.631 −30.337 92.823 1.00 47.45 ATOM 932 O VAL 270 41.651 −30.994 92.606 1.00 47.66 ATOM 933 N VAL 271 39.790 −29.948 91.864 1.00 45.27 ATOM 934 CA VAL 271 40.012 −30.290 90.461 1.00 42.45 ATOM 935 CB VAL 271 38.878 −31.202 89.925 1.00 41.54 ATOM 936 CG1 VAL 271 39.220 −31.677 88.530 1.00 39.33 ATOM 937 CG2 VAL 271 38.663 −32.380 90.857 1.00 40.44 ATOM 938 C VAL 271 40.123 −29.071 89.535 1.00 40.87 ATOM 939 O VAL 271 39.324 −28.132 89.623 1.00 41.07 ATOM 940 N ILE 272 41.130 −29.096 88.662 1.00 37.99 ATOM 941 CA ILE 272 41.342 −28.035 87.691 1.00 35.44 ATOM 942 CB ILE 272 42.724 −27.352 87.867 1.00 32.95 ATOM 943 CG2 ILE 272 42.894 −26.892 89.302 1.00 30.53 ATOM 944 CG1 ILE 272 43.857 −28.308 87.528 1.00 30.50 ATOM 945 CD1 ILE 272 45.218 −27.694 87.759 1.00 28.89 ATOM 946 C ILE 272 41.226 −28.705 86.329 1.00 36.01 ATOM 947 O ILE 272 41.804 −29.760 86.104 1.00 36.26 ATOM 948 N ARG 273 40.436 −28.100 85.444 1.00 36.70 ATOM 949 CA ARG 273 40.173 −28.629 84.107 1.00 36.68 ATOM 950 CB ARG 273 38.711 −29.077 83.996 1.00 34.08 ATOM 951 CG ARG 273 38.209 −30.035 85.056 1.00 32.56 ATOM 952 CD ARG 273 36.708 −30.273 84.871 1.00 32.51 ATOM 953 NE ARG 273 36.253 −31.508 85.502 1.00 31.47 ATOM 954 CZ ARG 273 36.149 −31.672 86.811 1.00 32.01 ATOM 955 NH1 ARG 273 36.458 −30.672 87.615 1.00 34.75 ATOM 956 NH2 ARG 273 35.771 −32.835 87.323 1.00 30.95 ATOM 957 C ARG 273 40.409 −27.566 83.030 1.00 39.20 ATOM 958 O ARG 273 40.272 −26.364 83.288 1.00 41.19 ATOM 959 N SER 274 40.757 −28.013 81.823 1.00 40.06 ATOM 960 CA SER 274 40.969 −27.114 80.691 1.00 40.76 ATOM 961 CB SER 274 42.332 −26.436 80.763 1.00 36.80 ATOM 962 OG SER 274 42.480 −25.540 79.681 1.00 32.87 ATOM 963 C SER 274 40.867 −27.899 79.399 1.00 43.92 ATOM 964 O SER 274 41.114 −29.100 79.372 1.00 45.39 ATOM 965 N CYS 275 40.480 −27.230 78.325 1.00 47.15 ATOM 966 CA CYS 275 40.377 −27.916 77.055 1.00 51.92 ATOM 967 C CYS 275 41.737 −27.968 76.403 1.00 52.82 ATOM 968 O CYS 275 41.890 −28.485 75.303 1.00 54.44 ATOM 969 CB CYS 275 39.375 −27.207 76.154 1.00 55.95 ATOM 970 SG CYS 275 37.681 −27.472 76.771 1.00 66.91 ATOM 971 N ASN 276 42.730 −27.439 77.106 1.00 53.33 ATOM 972 CA ASN 276 44.104 −27.397 76.624 1.00 52.97 ATOM 973 CB ASN 276 44.161 −26.855 75.186 1.00 55.96 ATOM 974 CG ASN 276 45.584 −26.683 74.685 1.00 61.01 ATOM 975 OD1 ASN 276 46.331 −25.861 75.210 1.00 63.58 ATOM 976 ND2 ASN 276 45.980 −27.485 73.701 1.00 64.98 ATOM 977 C ASN 276 44.864 −26.475 77.571 1.00 51.50 ATOM 978 O ASN 276 44.876 −25.251 77.398 1.00 50.11 ATOM 979 N PHE 277 45.483 −27.074 78.584 1.00 49.28 ATOM 980 CA PHE 277 46.235 −26.309 79.570 1.00 47.85 ATOM 981 CB PHE 277 46.763 −27.231 80.675 1.00 46.32 ATOM 982 CG PHE 277 45.689 −27.794 81.567 1.00 44.69 ATOM 983 CD1 PHE 277 45.136 −29.050 81.321 1.00 43.74 ATOM 984 CD2 PHE 277 45.235 −27.070 82.667 1.00 43.64 ATOM 985 CE1 PHE 277 44.149 −29.577 82.163 1.00 41.58 ATOM 986 CE2 PHE 277 44.249 −27.590 83.511 1.00 42.49 ATOM 987 CZ PHE 277 43.707 −28.848 83.258 1.00 40.91 ATOM 988 C PHE 277 47.397 −25.526 78.959 1.00 47.27 ATOM 989 O PHE 277 47.758 −24.456 79.451 1.00 46.87 ATOM 990 N THR 278 47.972 −26.069 77.890 1.00 47.46 ATOM 991 CA THR 278 49.103 −25.462 77.189 1.00 48.47 ATOM 992 CB THR 278 49.612 −26.414 76.092 1.00 48.42 ATOM 993 OG1 THR 278 50.438 −27.415 76.691 1.00 48.33 ATOM 994 CG2 THR 278 50.410 −25.659 75.038 1.00 49.75 ATOM 995 C THR 278 48.784 −24.103 76.562 1.00 48.99 ATOM 996 O THR 278 49.596 −23.168 76.609 1.00 48.80 ATOM 997 N ASP 279 47.600 −24.021 75.964 1.00 48.66 ATOM 998 CA ASP 279 47.094 −22.816 75.315 1.00 48.23 ATOM 999 CB ASP 279 45.819 −23.178 74.547 1.00 50.23 ATOM 1000 CG ASP 279 45.261 −22.025 73.742 1.00 51.68 ATOM 1001 OD1 ASP 279 44.294 −22.275 72.986 1.00 51.77 ATOM 1002 OD2 ASP 279 45.778 −20.890 73.870 1.00 51.55 ATOM 1003 C ASP 279 46.792 −21.801 76.414 1.00 47.12 ATOM 1004 O ASP 279 45.827 −21.958 77.168 1.00 47.67 ATOM 1005 N ASN 280 47.609 −20.758 76.507 1.00 43.96 ATOM 1006 CA ASN 280 47.410 −19.775 77.559 1.00 41.43 ATOM 1007 CB ASN 280 48.671 −18.910 77.722 1.00 39.74 ATOM 1008 CG ASN 280 49.007 −18.101 76.485 1.00 36.68 ATOM 1009 OD1 ASN 280 48.755 −18.525 75.364 1.00 36.56 ATOM 1010 ND2 ASN 280 49.604 −16.931 76.692 1.00 33.53 ATOM 1011 C ASN 280 46.174 −18.916 77.364 1.00 41.24 ATOM 1012 O ASN 280 45.970 −17.927 78.058 1.00 40.99 ATOM 1013 N ALA 281 45.321 −19.315 76.434 1.00 41.19 ATOM 1014 CA ALA 281 44.117 −18.547 76.192 1.00 40.89 ATOM 1015 CB ALA 281 44.119 −18.045 74.777 1.00 42.27 ATOM 1016 C ALA 281 42.859 −19.356 76.463 1.00 40.32 ATOM 1017 O ALA 281 41.764 −18.949 76.090 1.00 41.07 ATOM 1018 N LYS 282 43.012 −20.500 77.115 1.00 39.16 ATOM 1019 CA LYS 282 41.864 −21.334 77.423 1.00 38.60 ATOM 1020 CB LYS 282 42.116 −22.773 76.970 1.00 39.99 ATOM 1021 CG LYS 282 41.897 −22.990 75.479 1.00 41.46 ATOM 1022 CD LYS 282 40.523 −22.473 75.048 1.00 43.09 ATOM 1023 CE LYS 282 40.172 −22.875 73.625 1.00 41.82 ATOM 1024 NZ LYS 282 39.986 −24.349 73.519 1.00 42.86 ATOM 1025 C LYS 282 41.488 −21.310 78.897 1.00 37.93 ATOM 1026 O LYS 282 42.336 −21.477 79.777 1.00 38.22 ATOM 1027 N THR 283 40.200 −21.110 79.149 1.00 36.68 ATOM 1028 CA THR 283 39.648 −21.049 80.494 1.00 35.31 ATOM 1029 CB THR 283 38.117 −20.944 80.447 1.00 34.66 ATOM 1030 OG1 THR 283 37.745 −19.702 79.850 1.00 37.62 ATOM 1031 CG2 THR 283 37.523 −21.018 81.833 1.00 34.32 ATOM 1032 C THR 283 39.982 −22.263 81.340 1.00 35.03 ATOM 1033 O THR 283 39.808 −23.396 80.896 1.00 35.94 ATOM 1034 N ILE 284 40.461 −22.026 82.558 1.00 33.55 ATOM 1035 CA ILE 284 40.750 −23.115 83.481 1.00 32.06 ATOM 1036 CB ILE 284 42.087 −22.926 84.220 1.00 29.94 ATOM 1037 CG2 ILE 284 42.264 −24.025 85.253 1.00 25.00 ATOM 1038 CG1 ILE 284 43.234 −22.964 83.225 1.00 28.55 ATOM 1039 CD1 ILE 284 44.563 −22.787 83.859 1.00 28.55 ATOM 1040 C ILE 284 39.609 −23.124 84.502 1.00 33.37 ATOM 1041 O ILE 284 39.398 −22.149 85.237 1.00 32.79 ATOM 1042 N ILE 285 38.867 −24.227 84.516 1.00 33.28 ATOM 1043 CA ILE 285 37.740 −24.413 85.412 1.00 32.89 ATOM 1044 CB ILE 285 36.657 −25.259 84.734 1.00 31.95 ATOM 1045 CG2 ILE 285 35.537 −25.555 85.697 1.00 32.46 ATOM 1046 CG1 ILE 285 36.113 −24.517 83.527 1.00 32.81 ATOM 1047 CD1 ILE 285 34.981 −25.242 82.844 1.00 35.28 ATOM 1048 C ILE 285 38.158 −25.122 86.695 1.00 34.13 ATOM 1049 O ILE 285 38.440 −26.313 86.690 1.00 35.08 ATOM 1050 N VAL 286 38.206 −24.398 87.799 1.00 34.62 ATOM 1051 CA VAL 286 38.566 −25.024 89.056 1.00 34.98 ATOM 1052 CB VAL 286 39.403 −24.051 89.931 1.00 34.50 ATOM 1053 CG1 VAL 286 39.593 −24.600 91.335 1.00 31.43 ATOM 1054 CG2 VAL 286 40.743 −23.843 89.292 1.00 34.26 ATOM 1055 C VAL 286 37.276 −25.413 89.788 1.00 36.26 ATOM 1056 O VAL 286 36.276 −24.683 89.736 1.00 36.24 ATOM 1057 N GLN 287 37.290 −26.581 90.425 1.00 35.78 ATOM 1058 CA GLN 287 36.151 −27.041 91.210 1.00 36.32 ATOM 1059 CB GLN 287 35.441 −28.214 90.547 1.00 35.89 ATOM 1060 CG GLN 287 34.369 −28.830 91.444 1.00 35.81 ATOM 1061 CD GLN 287 33.732 −30.067 90.834 1.00 35.51 ATOM 1062 OE1 GLN 287 34.394 −30.838 90.141 1.00 34.61 ATOM 1063 NE2 GLN 287 32.446 −30.269 91.102 1.00 34.71 ATOM 1064 C GLN 287 36.673 −27.444 92.595 1.00 36.79 ATOM 1065 O GLN 287 37.691 −28.131 92.728 1.00 35.75 ATOM 1066 N LEU 288 35.955 −27.011 93.623 1.00 37.06 ATOM 1067 CA LEU 288 36.357 −27.248 94.996 1.00 37.17 ATOM 1068 CB LEU 288 36.146 −25.962 95.805 1.00 34.97 ATOM 1069 CG LEU 288 36.614 −24.630 95.206 1.00 32.83 ATOM 1070 CD1 LEU 288 35.969 −23.494 95.955 1.00 31.53 ATOM 1071 CD2 LEU 288 38.120 −24.514 95.268 1.00 31.88 ATOM 1072 C LEU 288 35.653 −28.405 95.707 1.00 38.46 ATOM 1073 O LEU 288 34.553 −28.817 95.334 1.00 38.22 ATOM 1074 N ASN 289 36.322 −28.898 96.748 1.00 39.95 ATOM 1075 CA ASN 289 35.855 −29.984 97.605 1.00 40.45 ATOM 1076 CB ASN 289 37.057 −30.772 98.117 1.00 40.55 ATOM 1077 CG ASN 289 38.027 −29.893 98.867 1.00 42.68 ATOM 1078 OD1 ASN 289 38.080 −28.692 98.600 1.00 43.84 ATOM 1079 ND2 ASN 289 38.797 −30.451 99.798 1.00 45.54 ATOM 1080 C ASN 289 35.136 −29.342 98.793 1.00 40.56 ATOM 1081 O ASN 289 34.426 −30.011 99.534 1.00 41.39 ATOM 1082 N THR 290 35.334 −28.037 98.971 1.00 40.82 ATOM 1083 CA THR 290 34.716 −27.293 100.075 1.00 39.80 ATOM 1084 CB THR 290 35.738 −26.968 101.168 1.00 40.22 ATOM 1085 OG1 THR 290 36.425 −28.160 101.564 1.00 40.45 ATOM 1086 CG2 THR 290 35.038 −26.345 102.361 1.00 40.96 ATOM 1087 C THR 290 34.141 −25.953 99.630 1.00 38.45 ATOM 1088 O THR 290 34.790 −25.211 98.898 1.00 38.51 ATOM 1089 N SER 291 32.941 −25.626 100.093 1.00 37.41 ATOM 1090 CA SER 291 32.334 −24.349 99.735 1.00 36.56 ATOM 1091 CB SER 291 30.834 −24.367 100.019 1.00 37.11 ATOM 1092 OG SER 291 30.126 −25.014 98.978 1.00 40.14 ATOM 1093 C SER 291 32.965 −23.232 100.537 1.00 35.66 ATOM 1094 O SER 291 33.504 −23.480 101.604 1.00 36.84 ATOM 1095 N VAL 292 32.919 −22.012 100.002 1.00 35.35 ATOM 1096 CA VAL 292 33.432 −20.806 100.682 1.00 34.01 ATOM 1097 CB VAL 292 34.734 −20.239 100.018 1.00 32.71 ATOM 1098 CG1 VAL 292 35.059 −18.859 100.597 1.00 27.63 ATOM 1099 CG2 VAL 292 35.907 −21.193 100.257 1.00 29.57 ATOM 1100 C VAL 292 32.306 −19.784 100.537 1.00 33.54 ATOM 1101 O VAL 292 31.983 −19.374 99.426 1.00 33.35 ATOM 1102 N GLU 293 31.691 −19.379 101.639 1.00 33.37 ATOM 1103 CA GLU 293 30.580 −18.440 101.519 1.00 34.15 ATOM 1104 CB GLU 293 29.834 −18.262 102.846 1.00 37.09 ATOM 1105 CG GLU 293 29.612 −19.536 103.649 1.00 44.11 ATOM 1106 CD GLU 293 30.893 −20.000 104.321 1.00 50.19 ATOM 1107 OE1 GLU 293 31.452 −19.216 105.135 1.00 53.93 ATOM 1108 OE2 GLU 293 31.350 −21.131 104.033 1.00 51.72 ATOM 1109 C GLU 293 31.013 −17.077 101.036 1.00 32.44 ATOM 1110 O GLU 293 32.131 −16.632 101.270 1.00 32.48 ATOM 1111 N ILE 294 30.112 −16.419 100.334 1.00 31.24 ATOM 1112 CA ILE 294 30.371 −15.080 99.858 1.00 31.02 ATOM 1113 CB ILE 294 30.909 −15.060 98.407 1.00 28.57 ATOM 1114 CG2 ILE 294 29.896 −15.631 97.459 1.00 28.94 ATOM 1115 CG1 ILE 294 31.228 −13.627 97.999 1.00 26.61 ATOM 1116 CD1 ILE 294 31.771 −13.513 96.622 1.00 26.35 ATOM 1117 C ILE 294 29.018 −14.391 99.953 1.00 32.34 ATOM 1118 O ILE 294 28.050 −14.785 99.293 1.00 31.74 ATOM 1119 N ASN 295 28.943 −13.381 100.811 1.00 33.69 ATOM 1120 CA ASN 295 27.694 −12.666 101.002 1.00 36.46 ATOM 1121 CB ASN 295 27.305 −12.678 102.484 1.00 36.40 ATOM 1122 CG ASN 295 27.390 −14.059 103.099 1.00 36.18 ATOM 1123 OD1 ASN 295 26.783 −15.025 102.619 1.00 32.60 ATOM 1124 ND2 ASN 295 28.148 −14.155 104.180 1.00 37.07 ATOM 1125 C ASN 295 27.801 −11.230 100.513 1.00 37.74 ATOM 1126 O ASN 295 28.729 −10.512 100.889 1.00 37.01 ATOM 1127 N CYS 296 26.852 −10.822 99.672 1.00 39.54 ATOM 1128 CA CYS 296 26.853 −9.467 99.142 1.00 40.74 ATOM 1129 C CYS 296 25.546 −8.761 99.438 1.00 39.17 ATOM 1130 O CYS 296 24.554 −9.388 99.804 1.00 37.88 ATOM 1131 CB CYS 296 27.051 −9.468 97.637 1.00 43.38 ATOM 1132 SG CYS 296 28.393 −10.504 96.984 1.00 50.13 ATOM 1133 N THR 297 25.548 −7.450 99.241 1.00 38.11 ATOM 1134 CA THR 297 24.368 −6.654 99.498 1.00 38.11 ATOM 1135 CB THR 297 24.326 −6.200 100.953 1.00 39.36 ATOM 1136 OG1 THR 297 23.087 −5.522 101.209 1.00 40.89 ATOM 1137 CG2 THR 297 25.500 −5.261 101.241 1.00 37.42 ATOM 1138 C THR 297 24.348 −5.412 98.629 1.00 37.88 ATOM 1139 O THR 297 25.400 −4.820 98.356 1.00 37.71 ATOM 1140 N GLY 298 23.144 −5.011 98.218 1.00 36.98 ATOM 1141 CA GLY 298 22.990 −3.829 97.389 1.00 36.14 ATOM 1142 C GLY 298 23.541 −2.583 98.058 1.00 35.80 ATOM 1143 O GLY 298 23.479 −1.486 97.499 1.00 35.86 ATOM 1144 N ALA 299 24.079 −2.752 99.262 1.00 35.67 ATOM 1145 CA ALA 299 24.648 −1.644 100.018 1.00 34.99 ATOM 1146 CB ALA 299 24.757 −2.001 101.506 1.00 35.85 ATOM 1147 C ALA 299 26.014 −1.346 99.450 1.00 34.21 ATOM 1148 O ALA 299 26.628 −0.354 99.809 1.00 34.18 ATOM 1149 N GLY 329 26.503 −2.232 98.591 1.00 34.17 ATOM 1150 CA GLY 329 27.785 −1.988 97.965 1.00 35.52 ATOM 1151 C GLY 329 28.940 −2.931 98.199 1.00 36.98 ATOM 1152 O GLY 329 30.059 −2.611 97.805 1.00 37.25 ATOM 1153 N HIS 330 28.709 −4.086 98.817 1.00 39.63 ATOM 1154 CA HIS 330 29.827 −5.002 99.058 1.00 40.25 ATOM 1155 CB HIS 330 30.600 −4.559 100.305 1.00 39.30 ATOM 1156 CG HIS 330 29.818 −4.666 101.578 1.00 40.80 ATOM 1157 CD2 HIS 330 30.171 −5.105 102.807 1.00 42.00 ATOM 1158 ND1 HIS 330 28.516 −4.227 101.693 1.00 41.71 ATOM 1159 CE1 HIS 330 28.105 −4.386 102.936 1.00 41.88 ATOM 1160 NE2 HIS 330 29.090 −4.918 103.636 1.00 42.53 ATOM 1161 C HIS 330 29.536 −6.504 99.162 1.00 40.37 ATOM 1162 O HIS 330 28.388 −6.961 99.125 1.00 38.87 ATOM 1163 N CYS 331 30.630 −7.255 99.255 1.00 41.78 ATOM 1164 CA CYS 331 30.620 −8.702 99.394 1.00 42.53 ATOM 1165 C CYS 331 31.656 −9.068 100.444 1.00 41.74 ATOM 1166 O CYS 331 32.783 −8.569 100.418 1.00 40.56 ATOM 1167 CB CYS 331 31.022 −9.387 98.105 1.00 44.95 ATOM 1168 SG CYS 331 29.923 −9.199 96.679 1.00 48.68 ATOM 1169 N ASN 332 31.273 −9.945 101.359 1.00 40.38 ATOM 1170 CA ASN 332 32.189 −10.364 102.386 1.00 40.12 ATOM 1171 CB ASN 332 31.556 −10.224 103.766 1.00 42.37 ATOM 1172 CG ASN 332 31.322 −8.777 104.151 1.00 44.33 ATOM 1173 OD1 ASN 332 32.169 −7.911 103.909 1.00 44.82 ATOM 1174 ND2 ASN 332 30.175 −8.509 104.768 1.00 44.71 ATOM 1175 C ASN 332 32.586 −11.795 102.141 1.00 39.72 ATOM 1176 O ASN 332 31.793 −12.607 101.661 1.00 38.64 ATOM 1177 N ILE 333 33.834 −12.088 102.472 1.00 40.00 ATOM 1178 CA ILE 333 34.387 −13.416 102.317 1.00 40.51 ATOM 1179 CB ILE 333 35.109 −13.544 100.985 1.00 40.85 ATOM 1180 CG2 ILE 333 35.936 −14.821 100.957 1.00 42.34 ATOM 1181 CG1 ILE 333 34.089 −13.520 99.855 1.00 40.11 ATOM 1182 CD1 ILE 333 34.709 −13.314 98.515 1.00 41.51 ATOM 1183 C ILE 333 35.381 −13.647 103.432 1.00 40.36 ATOM 1184 O ILE 333 36.201 −12.780 103.723 1.00 40.87 ATOM 1185 N ALA 334 35.299 −14.812 104.060 1.00 39.60 ATOM 1186 CA ALA 334 36.204 −15.156 105.147 1.00 38.54 ATOM 1187 CB ALA 334 35.762 −16.471 105.757 1.00 41.22 ATOM 1189 C ALA 334 37.614 −15.275 104.590 1.00 36.87 ATOM 1190 O ALA 334 37.883 −16.097 103.715 1.00 33.76 ATOM 1191 N ARG 335 38.510 −14.444 105.102 1.00 36.58 ATOM 1192 CA ARG 335 39.883 −14.434 104.628 1.00 37.37 ATOM 1193 CB ARG 335 40.669 −13.333 105.326 1.00 36.39 ATOM 1194 CG ARG 335 42.094 −13.213 104.847 1.00 38.55 ATOM 1195 CD ARG 335 42.801 −12.047 105.516 1.00 42.33 ATOM 1196 NE ARG 335 42.268 −10.762 105.079 1.00 44.44 ATOM 1197 CZ ARG 335 42.375 −10.305 103.837 1.00 45.53 ATOM 1198 NH1 ARG 335 42.999 −11.034 102.924 1.00 46.03 ATOM 1199 NH2 ARG 335 41.856 −9.127 103.509 1.00 46.38 ATOM 1200 C ARG 335 40.558 −15.774 104.855 1.00 38.44 ATOM 1201 O ARG 335 41.318 −16.259 104.012 1.00 39.73 ATOM 1202 N ALA 336 40.276 −16.375 106.000 1.00 38.31 ATOM 1203 CA ALA 336 40.849 −17.664 106.347 1.00 38.08 ATOM 1204 CB ALA 336 40.436 −18.025 107.750 1.00 38.47 ATOM 1205 C ALA 336 40.393 −18.754 105.371 1.00 38.68 ATOM 1206 O ALA 336 41.214 −19.420 104.728 1.00 37.19 ATOM 1207 N LYS 337 39.078 −18.934 105.271 1.00 39.27 ATOM 1208 CA LYS 337 38.523 −19.932 104.376 1.00 39.56 ATOM 1209 CB LYS 337 37.003 −19.839 104.339 1.00 40.15 ATOM 1210 CG LYS 337 36.316 −20.161 105.642 1.00 42.29 ATOM 1211 CD LYS 337 34.875 −20.564 105.373 1.00 44.78 ATOM 1212 CE LYS 337 34.130 −20.917 106.647 1.00 46.19 ATOM 1213 NZ LYS 337 32.829 −21.580 106.331 1.00 47.33 ATOM 1214 C LYS 337 39.066 −19.744 102.974 1.00 39.65 ATOM 1215 O LYS 337 39.464 −20.699 102.329 1.00 39.54 ATOM 1216 N TRP 338 39.086 −18.506 102.501 1.00 41.16 ATOM 1217 CA TRP 338 39.585 −18.252 101.159 1.00 43.17 ATOM 1218 CB TRP 338 39.319 −16.817 100.725 1.00 40.60 ATOM 1219 CG TRP 338 39.685 −16.593 99.290 1.00 37.38 ATOM 1220 CD2 TRP 338 38.950 −17.042 98.154 1.00 36.44 ATOM 1221 CE2 TRP 338 39.646 −16.608 97.004 1.00 36.35 ATOM 1222 CE3 TRP 338 37.765 −17.774 97.993 1.00 35.17 ATOM 1223 CD1 TRP 338 40.777 −15.928 98.803 1.00 36.91 ATOM 1224 NE1 TRP 338 40.761 −15.930 97.427 1.00 35.85 ATOM 1225 CZ2 TRP 338 39.194 −16.878 95.714 1.00 36.13 ATOM 1226 CZ3 TRP 338 37.316 −18.044 96.712 1.00 34.19 ATOM 1227 CH2 TRP 338 38.028 −17.596 95.588 1.00 35.36 ATOM 1228 C TRP 338 41.069 −18.515 101.032 1.00 46.01 ATOM 1229 O TRP 338 41.523 −19.094 100.045 1.00 46.74 ATOM 1230 N ASN 339 41.836 −18.083 102.020 1.00 48.56 ATOM 1231 CA ASN 339 43.260 −18.298 101.949 1.00 51.16 ATOM 1232 CB ASN 339 43.957 −17.688 103.143 1.00 56.16 ATOM 1233 CG ASN 339 45.435 −17.890 103.080 1.00 63.56 ATOM 1234 OD1 ASN 339 46.073 −17.445 102.132 1.00 64.19 ATOM 1235 ND2 ASN 339 45.995 −18.566 104.079 1.00 71.86 ATOM 1236 C ASN 339 43.605 −19.777 101.860 1.00 50.86 ATOM 1237 O ASN 339 44.597 −20.144 101.242 1.00 50.87 ATOM 1238 N ASN 340 42.800 −20.634 102.478 1.00 50.99 ATOM 1239 CA ASN 340 43.071 −22.067 102.407 1.00 51.70 ATOM 1240 CB ASN 340 42.192 −22.862 103.371 1.00 54.49 ATOM 1241 CG ASN 340 42.634 −22.724 104.808 1.00 58.41 ATOM 1242 OD1 ASN 340 43.787 −23.014 105.151 1.00 60.24 ATOM 1243 ND2 ASN 340 41.719 −22.288 105.666 1.00 60.46 ATOM 1244 C ASN 340 42.781 −22.540 101.004 1.00 50.85 ATOM 1245 O ASN 340 43.537 −23.331 100.433 1.00 51.84 ATOM 1246 N THR 341 41.669 −22.058 100.456 1.00 48.01 ATOM 1247 CA THR 341 41.269 −22.434 99.116 1.00 45.14 ATOM 1248 CB THR 341 39.989 −21.678 98.686 1.00 44.64 ATOM 1249 OG1 THR 341 38.964 −21.883 99.667 1.00 42.76 ATOM 1250 CG2 THR 341 39.488 −22.189 97.334 1.00 42.30 ATOM 1251 C THR 341 42.416 −22.124 98.163 1.00 44.38 ATOM 1252 O THR 341 42.821 −22.977 97.377 1.00 42.42 ATOM 1253 N LEU 342 42.959 −20.911 98.249 1.00 44.37 ATOM 1254 CA LEU 342 44.061 −20.531 97.373 1.00 44.41 ATOM 1255 CB LEU 342 44.506 −19.087 97.635 1.00 43.85 ATOM 1256 CG LEU 342 43.507 −17.950 97.335 1.00 44.37 ATOM 1257 CD1 LEU 342 44.162 −16.606 97.623 1.00 43.63 ATOM 1258 CD2 LEU 342 43.050 −17.996 95.894 1.00 43.05 ATOM 1259 C LEU 342 45.245 −21.489 97.514 1.00 44.72 ATOM 1260 O LEU 342 45.858 −21.851 96.515 1.00 45.32 ATOM 1261 N LYS 343 45.567 −21.917 98.735 1.00 44.30 ATOM 1262 CA LYS 343 46.678 −22.854 98.921 1.00 43.59 ATOM 1263 CB LYS 343 46.928 −23.141 100.406 1.00 44.40 ATOM 1264 CG LYS 343 48.240 −23.898 100.658 1.00 46.15 ATOM 1265 CD LYS 343 48.413 −24.323 102.114 1.00 49.16 ATOM 1266 CE LYS 343 48.578 −23.136 103.080 1.00 52.93 ATOM 1267 NZ LYS 343 49.893 −22.400 103.011 1.00 53.31 ATOM 1268 C LYS 343 46.388 −24.173 98.206 1.00 42.93 ATOM 1269 O LYS 343 47.242 −24.709 97.493 1.00 42.92 ATOM 1270 N GLN 344 45.179 −24.693 98.396 1.00 42.56 ATOM 1271 CA GLN 344 44.778 −25.957 97.777 1.00 42.99 ATOM 1272 CB GLN 344 43.385 −26.373 98.241 1.00 41.89 ATOM 1273 CG GLN 344 43.168 −26.344 99.725 1.00 42.51 ATOM 1274 CD GLN 344 41.735 −26.664 100.081 1.00 43.88 ATOM 1275 OE1 GLN 344 41.243 −27.736 99.755 1.00 45.09 ATOM 1276 NE2 GLN 344 41.052 −25.728 100.744 1.00 44.66 ATOM 1277 C GLN 344 44.762 −25.908 96.254 1.00 43.37 ATOM 1278 O GLN 344 44.870 −26.952 95.612 1.00 44.99 ATOM 1279 N ILE 345 44.602 −24.714 95.679 1.00 43.39 ATOM 1280 CA ILE 345 44.559 −24.567 94.218 1.00 42.52 ATOM 1281 CB ILE 345 43.705 −23.359 93.765 1.00 40.62 ATOM 1282 CG2 ILE 345 43.479 −23.434 92.280 1.00 39.28 ATOM 1283 CG1 ILE 345 42.332 −23.377 94.419 1.00 40.32 ATOM 1284 CD1 ILE 345 41.517 −22.134 94.104 1.00 40.02 ATOM 1285 C ILE 345 45.946 −24.394 93.611 1.00 43.06 ATOM 1286 O ILE 345 46.281 −25.050 92.626 1.00 42.31 ATOM 1287 N ALA 346 46.745 −23.496 94.184 1.00 44.37 ATOM 1288 CA ALA 346 48.097 −23.273 93.683 1.00 45.42 ATOM 1289 CB ALA 346 48.836 −22.275 94.556 1.00 43.26 ATOM 1290 C ALA 346 48.771 −24.630 93.743 1.00 46.84 ATOM 1291 O ALA 346 49.582 −24.981 92.886 1.00 47.39 ATOM 1292 N SER 347 48.408 −25.396 94.765 1.00 47.70 ATOM 1293 CA SER 347 48.950 −26.722 94.934 1.00 49.50 ATOM 1294 CB SER 347 48.337 −27.376 96.160 1.00 51.28 ATOM 1295 OG SER 347 48.850 −28.685 96.317 1.00 56.57 ATOM 1296 C SER 347 48.662 −27.558 93.683 1.00 49.94 ATOM 1297 O SER 347 49.586 −28.029 93.030 1.00 50.34 ATOM 1298 N LYS 348 47.382 −27.728 93.351 1.00 50.78 ATOM 1299 CA LYS 348 46.962 −28.494 92.170 1.00 51.63 ATOM 1300 CB LYS 348 45.432 −28.577 92.098 1.00 51.50 ATOM 1301 CG LYS 348 44.791 −29.584 93.032 1.00 51.75 ATOM 1302 CD LYS 348 45.064 −30.988 92.556 1.00 50.85 ATOM 1303 CE LYS 348 44.542 −32.004 93.543 1.00 50.69 ATOM 1304 NZ LYS 348 44.944 −33.375 93.137 1.00 50.94 ATOM 1305 C LYS 348 47.463 −27.869 90.869 1.00 52.28 ATOM 1306 O LYS 348 47.585 −28.535 89.840 1.00 52.16 ATOM 1307 N LEU 349 47.738 −26.579 90.908 1.00 53.08 ATOM 1308 CA LEU 349 48.203 −25.921 89.713 1.00 55.10 ATOM 1309 CB LEU 349 48.002 −24.402 89.824 1.00 53.88 ATOM 1310 CG LEU 349 46.572 −23.855 89.720 1.00 50.78 ATOM 1311 CD1 LEU 349 46.600 −22.369 89.985 1.00 49.11 ATOM 1312 CD2 LEU 349 45.977 −24.134 88.345 1.00 47.99 ATOM 1313 C LEU 349 49.655 −26.259 89.402 1.00 57.08 ATOM 1314 O LEU 349 49.959 −26.620 88.270 1.00 57.54 ATOM 1315 N ARG 350 50.555 −26.159 90.383 1.00 59.82 ATOM 1316 CA ARG 350 51.961 −26.476 90.114 1.00 63.18 ATOM 1317 CB ARG 350 52.866 −26.042 91.266 1.00 64.31 ATOM 1318 CG ARG 350 52.410 −26.471 92.624 1.00 68.34 ATOM 1319 CD ARG 350 53.595 −26.540 93.563 1.00 72.56 ATOM 1320 NE ARG 350 54.525 −25.427 93.375 1.00 76.31 ATOM 1321 CZ ARG 350 55.714 −25.343 93.974 1.00 78.63 ATOM 1322 NH1 ARG 350 56.113 −26.308 94.798 1.00 78.98 ATOM 1323 NH2 ARG 350 56.511 −24.301 93.751 1.00 79.29 ATOM 1324 C ARG 350 52.125 −27.968 89.851 1.00 64.33 ATOM 1325 O ARG 350 53.102 −28.405 89.234 1.00 65.71 ATOM 1326 N GLU 351 51.148 −28.741 90.312 1.00 64.55 ATOM 1327 CA GLU 351 51.126 −30.180 90.112 1.00 63.62 ATOM 1328 CB GLU 351 49.963 −30.778 90.898 1.00 66.10 ATOM 1329 CG GLU 351 49.896 −32.290 90.914 1.00 70.44 ATOM 1330 CD GLU 351 48.652 −32.811 91.628 1.00 72.67 ATOM 1331 OE1 GLU 351 47.536 −32.631 91.090 1.00 74.72 ATOM 1332 OE2 GLU 351 48.787 −33.397 92.726 1.00 73.74 ATOM 1333 C GLU 351 50.941 −30.456 88.615 1.00 61.98 ATOM 1334 O GLU 351 51.096 −31.588 88.162 1.00 61.55 ATOM 1335 N GLN 352 50.602 −29.409 87.861 1.00 60.65 ATOM 1336 CA GLN 352 50.397 −29.505 86.415 1.00 59.13 ATOM 1337 CB GLN 352 48.942 −29.191 86.053 1.00 56.49 ATOM 1338 CG GLN 352 48.699 −29.115 84.545 1.00 53.84 ATOM 1339 CD GLN 352 47.501 −29.931 84.092 1.00 52.61 ATOM 1340 OE1 GLN 352 47.280 −30.122 82.895 1.00 49.99 ATOM 1341 NE2 GLN 352 46.722 −30.416 85.048 1.00 52.71 ATOM 1342 C GLN 352 51.320 −28.619 85.563 1.00 59.46 ATOM 1343 O GLN 352 51.494 −28.873 84.375 1.00 58.99 ATOM 1344 N PHE 353 51.908 −27.585 86.152 1.00 60.32 ATOM 1345 CA PHE 353 52.796 −26.714 85.390 1.00 62.07 ATOM 1346 CB PHE 353 52.262 −25.277 85.366 1.00 61.62 ATOM 1347 CG PHE 353 50.957 −25.129 84.641 1.00 61.43 ATOM 1348 CD1 PHE 353 49.752 −25.258 85.316 1.00 61.91 ATOM 1349 CD2 PHE 353 50.930 −24.905 83.268 1.00 62.10 ATOM 1350 CE1 PHE 353 48.532 −25.168 84.633 1.00 62.04 ATOM 1351 CE2 PHE 353 49.717 −24.815 82.576 1.00 61.69 ATOM 1352 CZ PHE 353 48.516 −24.948 83.261 1.00 61.58 ATOM 1353 C PHE 353 54.229 −26.713 85.915 1.00 64.18 ATOM 1354 O PHE 353 55.046 −25.880 85.511 1.00 65.29 ATOM 1355 N GLY 354 54.540 −27.642 86.812 1.00 64.51 ATOM 1356 CA GLY 354 55.888 −27.697 87.340 1.00 65.83 ATOM 1357 C GLY 354 55.948 −27.501 88.838 1.00 67.15 ATOM 1358 O GLY 354 55.746 −26.395 89.346 1.00 67.01 ATOM 1359 N ASN 355 56.237 −28.589 89.544 1.00 67.83 ATOM 1360 CA ASN 355 56.329 −28.576 90.994 1.00 68.59 ATOM 1361 CB ASN 355 56.573 −29.995 91.513 1.00 70.55 ATOM 1362 CG ASN 355 55.301 −30.841 91.533 1.00 72.72 ATOM 1363 OD1 ASN 355 55.353 −32.048 91.776 1.00 74.24 ATOM 1364 ND2 ASN 355 54.155 −30.208 91.290 1.00 72.93 ATOM 1365 C ASN 355 57.413 −27.644 91.509 1.00 68.43 ATOM 1366 O ASN 355 57.574 −27.480 92.716 1.00 69.01 ATOM 1367 N ASN 356 58.155 −27.032 90.597 1.00 67.89 ATOM 1368 CA ASN 356 59.214 −26.114 90.988 1.00 67.81 ATOM 1369 CB ASN 356 60.495 −26.427 90.209 1.00 68.67 ATOM 1370 CG ASN 356 61.021 −27.836 90.475 1.00 68.82 ATOM 1371 OD1 ASN 356 62.067 −28.223 89.956 1.00 68.37 ATOM 1372 ND2 ASN 356 60.294 −28.605 91.282 1.00 69.10 ATOM 1373 C ASN 356 58.756 −24.690 90.698 1.00 67.61 ATOM 1374 O ASN 356 59.399 −23.719 91.109 1.00 68.06 ATOM 1375 N LYS 357 57.632 −24.588 89.989 1.00 66.72 ATOM 1376 CA LYS 357 57.028 −23.308 89.603 1.00 64.44 ATOM 1377 CB LYS 357 55.979 −23.528 88.503 1.00 65.55 ATOM 1378 CG LYS 357 56.524 −23.915 87.138 1.00 66.86 ATOM 1379 CD LYS 357 57.287 −22.758 86.511 1.00 68.57 ATOM 1380 CE LYS 357 57.563 −22.990 85.033 1.00 69.07 ATOM 1381 NZ LYS 357 56.297 −23.017 84.250 1.00 69.35 ATOM 1382 C LYS 357 56.353 −22.582 90.769 1.00 61.58 ATOM 1383 O LYS 357 55.735 −23.211 91.630 1.00 61.43 ATOM 1384 N THR 358 56.463 −21.257 90.778 1.00 57.89 ATOM 1385 CA THR 358 55.851 −20.434 91.817 1.00 54.10 ATOM 1386 CB THR 358 56.721 −19.218 92.155 1.00 53.27 ATOM 1387 OG1 THR 358 57.983 −19.666 92.659 1.00 52.66 ATOM 1388 CG2 THR 358 56.045 −18.358 93.202 1.00 53.26 ATOM 1389 C THR 358 54.500 −19.944 91.317 1.00 51.75 ATOM 1390 O THR 358 54.412 −19.332 90.257 1.00 51.73 ATOM 1391 N ILE 359 53.452 −20.221 92.084 1.00 48.72 ATOM 1392 CA ILE 359 52.100 −19.832 91.707 1.00 45.84 ATOM 1393 CB ILE 359 51.054 −20.849 92.247 1.00 44.27 ATOM 1394 CG2 ILE 359 49.667 −20.470 91.782 1.00 43.26 ATOM 1395 CG1 ILE 359 51.387 −22.258 91.767 1.00 42.29 ATOM 1396 CD1 ILE 359 51.461 −22.383 90.264 1.00 42.14 ATOM 1397 C ILE 359 51.732 −18.450 92.228 1.00 45.04 ATOM 1398 O ILE 359 51.703 −18.231 93.438 1.00 44.85 ATOM 1399 N ILE 360 51.451 −17.528 91.309 1.00 44.16 ATOM 1400 CA ILE 360 51.058 −16.163 91.667 1.00 43.62 ATOM 1401 CB ILE 360 51.930 −15.086 90.968 1.00 41.87 ATOM 1402 CG2 ILE 360 51.486 −13.711 91.399 1.00 41.80 ATOM 1403 CG1 ILE 360 53.401 −15.280 91.297 1.00 40.00 ATOM 1404 CD1 ILE 360 54.176 −15.839 90.143 1.00 41.00 ATOM 1405 C ILE 360 49.620 −15.898 91.231 1.00 43.95 ATOM 1406 O ILE 360 49.205 −16.302 90.139 1.00 43.81 ATOM 1407 N PHE 361 48.859 −15.215 92.076 1.00 43.88 ATOM 1408 CA PHE 361 47.486 −14.886 91.721 1.00 45.05 ATOM 1409 CB PHE 361 46.510 −15.333 92.818 1.00 44.55 ATOM 1410 CG PHE 361 46.421 −16.832 92.991 1.00 43.16 ATOM 1411 CD1 PHE 361 47.047 −17.463 94.059 1.00 41.83 ATOM 1412 CD2 PHE 361 45.723 −17.609 92.074 1.00 41.08 ATOM 1413 CE1 PHE 361 46.978 −18.835 94.207 1.00 39.99 ATOM 1414 CE2 PHE 361 45.650 −18.978 92.216 1.00 39.19 ATOM 1415 CZ PHE 361 46.280 −19.591 93.284 1.00 39.63 ATOM 1416 C PHE 361 47.370 −13.381 91.521 1.00 45.78 ATOM 1417 O PHE 361 47.599 −12.619 92.456 1.00 48.15 ATOM 1418 N LYS 362 47.032 −12.946 90.310 1.00 44.97 ATOM 1419 CA LYS 362 46.880 −11.519 90.044 1.00 45.08 ATOM 1420 CB LYS 362 47.836 −11.058 88.946 1.00 46.05 ATOM 1421 CG LYS 362 49.297 −11.075 89.307 1.00 46.12 ATOM 1422 CD LYS 362 50.116 −10.559 88.147 1.00 44.35 ATOM 1423 CE LYS 362 51.572 −10.516 88.524 1.00 45.15 ATOM 1424 NZ LYS 362 51.752 −9.677 89.742 1.00 45.33 ATOM 1425 C LYS 362 45.461 −11.179 89.611 1.00 45.45 ATOM 1426 O LYS 362 44.719 −12.042 89.138 1.00 45.50 ATOM 1427 N GLN 363 45.102 −9.907 89.759 1.00 45.24 ATOM 1428 CA GLN 363 43.781 −9.411 89.380 1.00 44.82 ATOM 1429 CB GLN 363 43.639 −7.954 89.818 1.00 44.59 ATOM 1430 CG GLN 363 44.807 −7.064 89.415 1.00 45.02 ATOM 1431 CD GLN 363 44.428 −5.595 89.372 1.00 45.87 ATOM 1432 OE1 GLN 363 43.555 −5.199 88.600 1.00 47.42 ATOM 1433 NE2 GLN 363 45.079 −4.780 90.199 1.00 44.92 ATOM 1434 C GLN 363 43.527 −9.506 87.872 1.00 45.01 ATOM 1435 O GLN 363 44.459 −9.717 87.090 1.00 44.87 ATOM 1436 N SER 364 42.263 −9.350 87.470 1.00 44.60 ATOM 1437 CA SER 364 41.895 −9.394 86.052 1.00 43.07 ATOM 1438 CB SER 364 40.444 −8.956 85.850 1.00 41.38 ATOM 1439 OG SER 364 40.073 −9.076 84.487 1.00 39.74 ATOM 1440 C SER 364 42.803 −8.436 85.297 1.00 43.26 ATOM 1441 O SER 364 43.104 −7.347 85.793 1.00 43.43 ATOM 1442 N SER 365 43.234 −8.829 84.102 1.00 42.44 ATOM 1443 CA SER 365 44.116 −7.979 83.312 1.00 41.33 ATOM 1444 CB SER 365 45.140 −8.846 82.566 1.00 41.58 ATOM 1445 OG SER 365 44.530 −10.000 82.013 1.00 44.41 ATOM 1446 C SER 365 43.445 −6.996 82.328 1.00 40.25 ATOM 1447 O SER 365 44.132 −6.413 81.491 1.00 42.93 ATOM 1448 N GLY 366 42.130 −6.794 82.424 1.00 36.76 ATOM 1449 CA GLY 366 41.473 −5.860 81.524 1.00 32.05 ATOM 1450 C GLY 366 40.321 −6.445 80.741 1.00 31.17 ATOM 1451 O GLY 366 40.099 −7.652 80.762 1.00 31.00 ATOM 1452 N GLY 367 39.581 −5.585 80.044 1.00 30.27 ATOM 1453 CA GLY 367 38.441 −6.040 79.258 1.00 29.70 ATOM 1454 C GLY 367 37.117 −5.504 79.777 1.00 29.80 ATOM 1455 O GLY 367 37.087 −4.691 80.702 1.00 31.08 ATOM 1456 N ASP 368 36.015 −5.954 79.192 1.00 29.13 ATOM 1457 CA ASP 368 34.699 −5.507 79.626 1.00 31.89 ATOM 1458 CB ASP 368 33.604 −6.305 78.909 1.00 35.79 ATOM 1459 CG ASP 368 33.588 −6.073 77.397 1.00 39.65 ATOM 1460 OD1 ASP 368 32.826 −6.784 76.700 1.00 40.00 ATOM 1461 OD2 ASP 368 34.328 −5.187 76.908 1.00 42.73 ATOM 1462 C ASP 368 34.527 −5.663 81.144 1.00 32.13 ATOM 1463 O ASP 368 35.139 −6.527 81.757 1.00 32.82 ATOM 1464 N PRO 369 33.684 −4.821 81.766 1.00 31.85 ATOM 1465 CD PRO 369 32.993 −3.693 81.120 1.00 30.96 ATOM 1466 CA PRO 369 33.404 −4.838 83.207 1.00 31.36 ATOM 1467 CB PRO 369 32.265 −3.842 83.337 1.00 31.63 ATOM 1468 CG PRO 369 32.613 −2.833 82.289 1.00 31.18 ATOM 1469 C PRO 369 33.007 −6.203 83.739 1.00 30.91 ATOM 1470 O PRO 369 33.485 −6.649 84.778 1.00 31.90 ATOM 1471 N GLU 370 32.112 −6.858 83.023 1.00 30.62 ATOM 1472 CA GLU 370 31.627 −8.162 83.415 1.00 31.59 ATOM 1473 CB GLU 370 30.534 −8.585 82.440 1.00 32.54 ATOM 1474 CG GLU 370 29.303 −7.659 82.445 1.00 34.81 ATOM 1475 CD GLU 370 29.452 −6.366 81.622 1.00 34.63 ATOM 1476 OE1 GLU 370 28.495 −5.567 81.601 1.00 34.16 ATOM 1477 OE2 GLU 370 30.503 −6.142 80.991 1.00 35.90 ATOM 1478 C GLU 370 32.718 −9.245 83.519 1.00 32.22 ATOM 1479 O GLU 370 32.528 −10.259 84.194 1.00 33.09 ATOM 1480 N ILE 371 33.857 −9.016 82.864 1.00 31.32 ATOM 1481 CA ILE 371 34.999 −9.943 82.861 1.00 28.31 ATOM 1482 CB ILE 371 35.579 −10.085 81.422 1.00 28.08 ATOM 1483 CG2 ILE 371 37.098 −10.089 81.437 1.00 27.78 ATOM 1484 CG1 ILE 371 35.037 −11.343 80.779 1.00 28.02 ATOM 1485 CD1 ILE 371 33.555 −11.407 80.819 1.00 30.47 ATOM 1486 C ILE 371 36.133 −9.506 83.797 1.00 27.21 ATOM 1487 O ILE 371 36.974 −10.315 84.191 1.00 26.14 ATOM 1488 N VAL 372 36.158 −8.224 84.138 1.00 26.33 ATOM 1489 CA VAL 372 37.194 −7.676 85.007 1.00 27.67 ATOM 1490 CB VAL 372 37.487 −6.200 84.678 1.00 27.14 ATOM 1491 CG1 VAL 372 38.468 −5.636 85.687 1.00 24.67 ATOM 1492 CG2 VAL 372 38.035 −6.078 83.258 1.00 26.38 ATOM 1493 C VAL 372 36.807 −7.739 86.467 1.00 28.75 ATOM 1494 O VAL 372 37.662 −7.792 87.355 1.00 29.82 ATOM 1495 N THR 373 35.506 −7.734 86.709 1.00 29.47 ATOM 1496 CA THR 373 34.983 −7.770 88.066 1.00 28.66 ATOM 1497 CB THR 373 34.079 −6.554 88.296 1.00 27.96 ATOM 1498 OG1 THR 373 32.916 −6.668 87.472 1.00 28.85 ATOM 1499 CG2 THR 373 34.801 −5.285 87.888 1.00 26.32 ATOM 1500 C THR 373 34.166 −9.042 88.221 1.00 28.00 ATOM 1501 O THR 373 33.806 −9.658 87.211 1.00 28.23 ATOM 1502 N HIS 374 33.902 −9.453 89.466 1.00 27.55 ATOM 1503 CA HIS 374 33.075 −10.642 89.723 1.00 26.55 ATOM 1504 CB HIS 374 33.245 −11.149 91.162 1.00 25.93 ATOM 1505 CG HIS 374 32.187 −12.121 91.591 1.00 26.09 ATOM 1506 CD2 HIS 374 31.358 −12.121 92.663 1.00 26.47 ATOM 1507 ND1 HIS 374 31.866 −13.243 90.863 1.00 27.70 ATOM 1508 CE1 HIS 374 30.881 −13.892 91.463 1.00 25.87 ATOM 1509 NE2 HIS 374 30.555 −13.232 92.557 1.00 25.26 ATOM 1510 C HIS 374 31.654 −10.153 89.476 1.00 25.07 ATOM 1511 O HIS 374 31.071 −9.423 90.268 1.00 25.98 ATOM 1512 N TRP 375 31.132 −10.546 88.332 1.00 24.08 ATOM 1513 CA TRP 375 29.829 −10.142 87.866 1.00 24.74 ATOM 1514 CB TRP 375 29.960 −9.781 86.383 1.00 25.04 ATOM 1515 CG TRP 375 28.702 −9.478 85.662 1.00 25.75 ATOM 1516 CD2 TRP 375 28.096 −10.271 84.645 1.00 25.29 ATOM 1517 CE2 TRP 375 26.916 −9.609 84.235 1.00 24.75 ATOM 1518 CE3 TRP 375 28.430 −11.488 84.037 1.00 26.21 ATOM 1519 CD1 TRP 375 27.896 −8.390 85.828 1.00 26.87 ATOM 1520 NE1 TRP 375 26.819 −8.457 84.972 1.00 25.73 ATOM 1521 CZ2 TRP 375 26.075 −10.111 83.256 1.00 25.28 ATOM 1522 CZ3 TRP 375 27.591 −11.996 83.057 1.00 25.89 ATOM 1523 CH2 TRP 375 26.424 −11.307 82.678 1.00 26.36 ATOM 1524 C TRP 375 28.844 −11.268 88.060 1.00 26.93 ATOM 1525 O TRP 375 29.098 −12.411 87.687 1.00 27.40 ATOM 1526 N PHE 376 27.707 −10.946 88.646 1.00 28.62 ATOM 1527 CA PHE 376 26.693 −11.954 88.863 1.00 31.15 ATOM 1528 CB PHE 376 26.989 −12.736 90.130 1.00 30.11 ATOM 1529 CG PHE 376 27.135 −11.877 91.332 1.00 30.51 ATOM 1530 CD1 PHE 376 28.310 −11.162 91.547 1.00 30.86 ATOM 1531 CD2 PHE 376 26.090 −11.754 92.241 1.00 30.19 ATOM 1532 CE1 PHE 376 28.448 −10.331 92.652 1.00 29.71 ATOM 1533 CE2 PHE 376 26.209 −10.929 93.352 1.00 30.22 ATOM 1534 CZ PHE 376 27.393 −10.213 93.560 1.00 30.89 ATOM 1535 C PHE 376 25.355 −11.279 88.996 1.00 32.83 ATOM 1536 O PHE 376 25.280 −10.086 89.252 1.00 33.02 ATOM 1537 N ASN 377 24.299 −12.051 88.809 1.00 35.69 ATOM 1538 CA ASN 377 22.963 −11.521 88.929 1.00 40.61 ATOM 1539 CB ASN 377 22.046 −12.178 87.913 1.00 44.38 ATOM 1540 CG ASN 377 20.647 −11.597 87.940 1.00 48.66 ATOM 1541 OD1 ASN 377 20.426 −10.443 87.542 1.00 48.26 ATOM 1542 ND2 ASN 377 19.689 −12.393 88.420 1.00 51.13 ATOM 1543 C ASN 377 22.491 −11.855 90.327 1.00 42.23 ATOM 1544 O ASN 377 22.892 −12.864 90.876 1.00 44.30 ATOM 1545 N CYS 378 21.643 −11.009 90.901 1.00 44.55 ATOM 1546 CA CYS 378 21.117 −11.220 92.251 1.00 45.14 ATOM 1547 C CYS 378 19.934 −10.282 92.488 1.00 43.00 ATOM 1548 O CYS 378 20.075 −9.066 92.377 1.00 41.28 ATOM 1549 CB CYS 378 22.203 −10.950 93.302 1.00 49.09 ATOM 1550 SG CYS 378 21.506 −11.015 94.982 1.00 57.12 ATOM 1551 N GLY 379 18.773 −10.842 92.819 1.00 41.22 ATOM 1552 CA GLY 379 17.600 −10.011 93.025 1.00 40.83 ATOM 1553 C GLY 379 17.246 −9.244 91.753 1.00 40.79 ATOM 1554 O GLY 379 16.556 −8.222 91.784 1.00 41.26 ATOM 1555 N GLY 380 17.718 −9.738 90.619 1.00 39.72 ATOM 1556 CA GLY 380 17.442 −9.059 89.372 1.00 39.79 ATOM 1557 C GLY 380 18.461 −7.986 89.005 1.00 39.81 ATOM 1558 O GLY 380 18.544 −7.578 87.842 1.00 39.98 ATOM 1559 N GLU 381 19.243 −7.524 89.979 1.00 39.10 ATOM 1560 CA GLU 381 20.244 −6.489 89.712 1.00 38.16 ATOM 1561 CB GLU 381 20.440 −5.607 90.940 1.00 38.52 ATOM 1562 CG GLU 381 19.162 −5.139 91.601 1.00 41.28 ATOM 1563 CD GLU 381 18.327 −4.226 90.728 1.00 43.40 ATOM 1564 OE1 GLU 381 18.904 −3.420 89.963 1.00 44.79 ATOM 1565 OE2 GLU 381 17.083 −4.303 90.827 1.00 44.94 ATOM 1566 C GLU 381 21.583 −7.123 89.353 1.00 36.75 ATOM 1567 O GLU 381 21.890 −8.228 89.796 1.00 34.31 ATOM 1568 N PHE 382 22.382 −6.421 88.556 1.00 34.93 ATOM 1569 CA PHE 382 23.684 −6.937 88.174 1.00 34.11 ATOM 1570 CB PHE 382 23.955 −6.685 86.699 1.00 35.03 ATOM 1571 CG PHE 382 23.062 −7.450 85.796 1.00 35.63 ATOM 1572 CD1 PHE 382 21.868 −6.901 85.351 1.00 37.48 ATOM 1573 CD2 PHE 382 23.392 −8.740 85.415 1.00 37.08 ATOM 1574 CE1 PHE 382 21.007 −7.628 84.534 1.00 38.27 ATOM 1575 CE2 PHE 382 22.543 −9.482 84.600 1.00 38.30 ATOM 1576 CZ PHE 382 21.343 −8.924 84.156 1.00 38.80 ATOM 1577 C PHE 382 24.800 −6.316 88.992 1.00 33.85 ATOM 1578 O PHE 382 25.066 −5.122 88.892 1.00 33.66 ATOM 1579 N PHE 383 25.463 −7.145 89.788 1.00 33.72 ATOM 1580 CA PHE 383 26.557 −6.694 90.628 1.00 33.09 ATOM 1581 CB PHE 383 26.646 −7.546 91.895 1.00 34.99 ATOM 1582 CG PHE 383 25.462 −7.409 92.806 1.00 38.33 ATOM 1583 CD1 PHE 383 24.183 −7.730 92.364 1.00 39.48 ATOM 1584 CD2 PHE 383 25.619 −6.928 94.103 1.00 40.16 ATOM 1585 CE1 PHE 383 23.079 −7.568 93.195 1.00 39.96 ATOM 1586 CE2 PHE 383 24.517 −6.762 94.942 1.00 39.80 ATOM 1587 CZ PHE 383 23.247 −7.082 94.484 1.00 40.07 ATOM 1588 C PHE 383 27.876 −6.775 89.887 1.00 31.86 ATOM 1589 O PHE 383 28.064 −7.627 89.024 1.00 30.97 ATOM 1590 N TYR 384 28.779 −5.870 90.233 1.00 31.42 ATOM 1591 CA TYR 384 30.102 −5.818 89.646 1.00 32.51 ATOM 1592 CB TYR 384 30.197 −4.673 88.643 1.00 33.51 ATOM 1593 CG TYR 384 29.350 −4.850 87.399 1.00 35.33 ATOM 1594 CD1 TYR 384 27.961 −4.728 87.451 1.00 36.88 ATOM 1595 CE1 TYR 384 27.177 −4.891 86.311 1.00 36.38 ATOM 1596 CD2 TYR 384 29.938 −5.145 86.170 1.00 35.34 ATOM 1597 CE2 TYR 384 29.165 −5.311 85.023 1.00 36.36 ATOM 1598 CZ TYR 384 27.784 −5.185 85.102 1.00 37.21 ATOM 1599 OH TYR 384 27.008 −5.351 83.971 1.00 37.53 ATOM 1600 C TYR 384 31.033 −5.558 90.815 1.00 33.55 ATOM 1601 O TYR 384 31.207 −4.404 91.217 1.00 32.94 ATOM 1602 N CYS 385 31.619 −6.631 91.356 1.00 34.77 ATOM 1603 CA CYS 385 32.509 −6.549 92.525 1.00 34.65 ATOM 1604 C CYS 385 33.971 −6.626 92.216 1.00 34.20 ATOM 1605 O CYS 385 34.433 −7.558 91.565 1.00 35.22 ATOM 1606 CB CYS 385 32.217 −7.658 93.521 1.00 34.87 ATOM 1607 SG CYS 385 30.526 −7.663 94.168 1.00 40.52 ATOM 1608 N ASN 386 34.705 −5.653 92.727 1.00 33.25 ATOM 1609 CA ASN 386 36.129 −5.598 92.521 1.00 33.13 ATOM 1610 CB ASN 386 36.645 −4.259 93.011 1.00 35.09 ATOM 1611 CG ASN 386 38.103 −4.104 92.775 1.00 39.37 ATOM 1612 OD1 ASN 386 38.880 −4.983 93.117 1.00 41.53 ATOM 1613 ND2 ASN 386 38.506 −2.990 92.194 1.00 43.99 ATOM 1614 C ASN 386 36.802 −6.744 93.280 1.00 32.07 ATOM 1615 O ASN 386 36.891 −6.718 94.507 1.00 33.16 ATOM 1616 N SER 387 37.288 −7.746 92.555 1.00 30.06 ATOM 1617 CA SER 387 37.922 −8.895 93.196 1.00 29.26 ATOM 1618 CB SER 387 37.505 −10.178 92.478 1.00 28.12 ATOM 1619 OG SER 387 37.730 −10.093 91.087 1.00 26.31 ATOM 1620 C SER 387 39.443 −8.867 93.337 1.00 29.50 ATOM 1621 O SER 387 40.063 −9.889 93.624 1.00 29.39 ATOM 1622 N THR 388 40.045 −7.702 93.159 1.00 29.97 ATOM 1623 CA THR 388 41.488 −7.586 93.273 1.00 31.62 ATOM 1624 CB THR 388 41.929 −6.116 93.190 1.00 32.80 ATOM 1625 OG1 THR 388 41.734 −5.630 91.849 1.00 31.68 ATOM 1626 CG2 THR 388 43.392 −5.980 93.590 1.00 31.85 ATOM 1627 C THR 388 42.038 −8.194 94.561 1.00 33.05 ATOM 1628 O THR 388 43.100 −8.816 94.553 1.00 33.91 ATOM 1629 N GLN 389 41.320 −8.027 95.667 1.00 34.67 ATOM 1630 CA GLN 389 41.792 −8.574 96.944 1.00 37.35 ATOM 1631 CB GLN 389 40.957 −8.065 98.124 1.00 36.04 ATOM 1632 CG GLN 389 40.860 −6.578 98.266 1.00 34.05 ATOM 1633 CD GLN 389 39.773 −6.202 99.241 1.00 34.91 ATOM 1634 OE1 GLN 389 39.964 −6.271 100.451 1.00 37.19 ATOM 1635 NE2 GLN 389 38.609 −5.826 98.720 1.00 36.20 ATOM 1636 C GLN 389 41.779 −10.101 97.011 1.00 38.08 ATOM 1637 O GLN 389 42.422 −10.687 97.882 1.00 40.01 ATOM 1638 N LEU 390 41.042 −10.752 96.124 1.00 37.43 ATOM 1639 CA LEU 390 40.994 −12.199 96.175 1.00 38.01 ATOM 1640 CB LEU 390 39.663 −12.699 95.613 1.00 37.92 ATOM 1641 CG LEU 390 38.396 −12.318 96.392 1.00 37.01 ATOM 1642 CD1 LEU 390 37.175 −12.765 95.614 1.00 35.68 ATOM 1643 CD2 LEU 390 38.399 −12.959 97.764 1.00 35.67 ATOM 1644 C LEU 390 42.163 −12.816 95.415 1.00 39.31 ATOM 1645 O LEU 390 42.692 −13.863 95.801 1.00 40.54 ATOM 1646 N PHE 391 42.583 −12.150 94.347 1.00 39.70 ATOM 1647 CA PHE 391 43.680 −12.644 93.528 1.00 38.54 ATOM 1648 CB PHE 391 43.206 −12.794 92.092 1.00 37.22 ATOM 1649 CG PHE 391 41.913 −13.532 91.984 1.00 37.31 ATOM 1650 CD1 PHE 391 40.707 −12.871 92.177 1.00 38.01 ATOM 1651 CD2 PHE 391 41.897 −14.907 91.784 1.00 37.44 ATOM 1652 CE1 PHE 391 39.507 −13.565 92.179 1.00 37.83 ATOM 1653 CE2 PHE 391 40.699 −15.613 91.786 1.00 37.13 ATOM 1654 CZ PHE 391 39.501 −14.939 91.986 1.00 38.34 ATOM 1655 C PHE 391 44.848 −11.691 93.622 1.00 39.15 ATOM 1656 O PHE 391 45.093 −10.874 92.724 1.00 37.81 ATOM 1657 N ASN 392 45.554 −11.808 94.742 1.00 40.04 ATOM 1658 CA ASN 392 46.709 −10.980 95.038 1.00 40.61 ATOM 1659 CB ASN 392 46.243 −9.647 95.650 1.00 40.52 ATOM 1660 CG ASN 392 47.401 −8.713 95.990 1.00 42.11 ATOM 1661 OD1 ASN 392 48.388 −8.643 95.255 1.00 42.90 ATOM 1662 ND2 ASN 392 47.272 −7.978 97.093 1.00 42.11 ATOM 1663 C ASN 392 47.615 −11.736 96.006 1.00 40.17 ATOM 1664 O ASN 392 47.771 −11.336 97.148 1.00 40.62 ATOM 1665 N SER 393 48.205 −12.837 95.558 1.00 40.28 ATOM 1666 CA SER 393 49.085 −13.598 96.436 1.00 41.43 ATOM 1667 CB SER 393 48.261 −14.448 97.403 1.00 40.63 ATOM 1668 OG SER 393 47.328 −15.262 96.718 1.00 40.80 ATOM 1669 C SER 393 50.077 −14.479 95.687 1.00 42.79 ATOM 1670 O SER 393 49.819 −14.908 94.556 1.00 42.31 ATOM 1671 N THR 394 51.212 −14.737 96.333 1.00 43.79 ATOM 1672 CA THR 394 52.277 −15.551 95.756 1.00 45.04 ATOM 1673 CB THR 394 53.574 −14.737 95.642 1.00 45.96 ATOM 1674 OG1 THR 394 53.333 −13.573 94.833 1.00 46.10 ATOM 1675 CG2 THR 394 54.688 −15.584 95.026 1.00 45.27 ATOM 1676 C THR 394 52.541 −16.790 96.602 1.00 45.64 ATOM 1677 O THR 394 52.906 −16.684 97.769 1.00 44.76 ATOM 1678 N TRP 395 52.378 −17.964 95.996 1.00 47.09 ATOM 1679 CA TRP 395 52.548 −19.228 96.705 1.00 47.76 ATOM 1680 CB TRP 395 51.288 −20.068 96.527 1.00 41.92 ATOM 1681 CG TRP 395 50.107 −19.326 96.976 1.00 38.28 ATOM 1682 CD2 TRP 395 49.405 −19.506 98.205 1.00 36.22 ATOM 1683 CE2 TRP 395 48.415 −18.503 98.268 1.00 36.46 ATOM 1684 CE3 TRP 395 49.514 −20.414 99.258 1.00 33.85 ATOM 1685 CD1 TRP 395 49.532 −18.258 96.357 1.00 37.38 ATOM 1686 NE1 TRP 395 48.517 −17.754 97.126 1.00 36.41 ATOM 1687 CZ2 TRP 395 47.539 −18.387 99.348 1.00 34.01 ATOM 1688 CZ3 TRP 395 48.647 −20.297 100.324 1.00 33.66 ATOM 1689 CH2 TRP 395 47.670 −19.290 100.361 1.00 33.40 ATOM 1690 C TRP 395 53.761 −20.066 96.339 1.00 51.43 ATOM 1691 O TRP 395 54.159 −20.124 95.170 1.00 52.73 ATOM 1692 N PHE 396 54.339 −20.710 97.358 1.00 54.22 ATOM 1693 CA PHE 396 55.491 −21.589 97.190 1.00 56.04 ATOM 1694 CB PHE 396 55.138 −22.681 96.186 1.00 54.94 ATOM 1695 CG PHE 396 53.790 −23.305 96.422 1.00 55.63 ATOM 1696 CD1 PHE 396 53.083 −23.883 95.373 1.00 56.03 ATOM 1697 CD2 PHE 396 53.226 −23.325 97.699 1.00 56.08 ATOM 1698 CE1 PHE 396 51.830 −24.480 95.591 1.00 56.77 ATOM 1699 CE2 PHE 396 51.974 −23.917 97.930 1.00 56.41 ATOM 1700 CZ PHE 396 51.275 −24.495 96.872 1.00 56.06 ATOM 1701 C PHE 396 56.708 −20.813 96.713 1.00 58.81 ATOM 1702 O PHE 396 57.523 −21.322 95.938 1.00 59.35 ATOM 1703 N ASN 397 56.815 −19.570 97.172 1.00 61.45 ATOM 1704 CA ASN 397 57.932 −18.717 96.802 1.00 63.89 ATOM 1705 CB ASN 397 57.462 −17.262 96.713 1.00 65.82 ATOM 1706 CG ASN 397 58.568 −16.310 96.270 1.00 68.51 ATOM 1707 OD1 ASN 397 58.333 −15.112 96.075 1.00 69.99 ATOM 1708 ND2 ASN 397 59.782 −16.839 96.110 1.00 68.62 ATOM 1709 C ASN 397 59.052 −18.854 97.837 1.00 64.94 ATOM 1710 O ASN 397 59.583 −19.946 98.065 1.00 64.91 ATOM 1711 N GLY 410 45.948 −11.180 107.879 1.00 61.02 ATOM 1712 CA GLY 410 45.413 −9.847 107.656 1.00 62.50 ATOM 1713 C GLY 410 44.155 −9.569 108.466 1.00 62.44 ATOM 1714 O GLY 410 44.097 −9.849 109.668 1.00 63.35 ATOM 1715 N SER 411 43.145 −9.007 107.814 1.00 61.14 ATOM 1716 CA SER 411 41.893 −8.720 108.488 1.00 60.04 ATOM 1717 CB SER 411 41.252 −7.461 107.913 1.00 61.29 ATOM 1718 OG SER 411 39.982 −7.232 108.499 1.00 62.93 ATOM 1719 C SER 411 40.959 −9.902 108.295 1.00 59.15 ATOM 1720 O SER 411 40.857 −10.448 107.197 1.00 59.05 ATOM 1721 N ASP 412 40.278 −10.285 109.369 1.00 57.82 ATOM 1722 CA ASP 412 39.338 −11.406 109.376 1.00 56.24 ATOM 1723 CB ASP 412 38.360 −11.213 110.532 1.00 59.37 ATOM 1724 CG ASP 412 37.032 −11.908 110.298 1.00 63.07 ATOM 1725 OD1 ASP 412 37.031 −13.136 110.041 1.00 64.07 ATOM 1726 OD2 ASP 412 35.990 −11.214 110.371 1.00 65.25 ATOM 1727 C ASP 412 38.556 −11.681 108.082 1.00 53.55 ATOM 1728 O ASP 412 38.694 −12.746 107.475 1.00 52.85 ATOM 1729 N THR 413 37.715 −10.735 107.680 1.00 50.45 ATOM 1730 CA THR 413 36.918 −10.892 106.472 1.00 46.99 ATOM 1731 CB THR 413 35.415 −10.527 106.742 1.00 46.65 ATOM 1732 OG1 THR 413 34.929 −9.666 105.703 1.00 46.90 ATOM 1733 CG2 THR 413 35.247 −9.813 108.078 1.00 44.53 ATOM 1734 C THR 413 37.456 −10.014 105.337 1.00 44.78 ATOM 1735 O THR 413 38.021 −8.954 105.580 1.00 45.19 ATOM 1736 N ILE 414 37.311 −10.471 104.099 1.00 41.90 ATOM 1737 CA ILE 414 37.744 −9.684 102.949 1.00 39.73 ATOM 1738 CB ILE 414 38.299 −10.564 101.813 1.00 38.13 ATOM 1739 CG2 ILE 414 38.798 −9.697 100.690 1.00 36.56 ATOM 1740 CG1 ILE 414 39.464 −11.408 102.316 1.00 37.94 ATOM 1741 CD1 ILE 414 39.966 −12.403 101.300 1.00 34.67 ATOM 1742 C ILE 414 36.474 −9.007 102.444 1.00 39.45 ATOM 1743 O ILE 414 35.541 −9.682 102.008 1.00 38.16 ATOM 1744 N THR 415 36.420 −7.683 102.526 1.00 39.33 ATOM 1745 CA THR 415 35.237 −6.956 102.071 1.00 39.02 ATOM 1746 CB THR 415 34.868 −5.782 103.045 1.00 40.55 ATOM 1747 OG1 THR 415 34.451 −6.313 104.313 1.00 41.85 ATOM 1748 CG2 THR 415 33.731 −4.942 102.483 1.00 39.85 ATOM 1749 C THR 415 35.487 −6.410 100.671 1.00 37.52 ATOM 1750 O THR 415 36.386 −5.592 100.458 1.00 36.96 ATOM 1751 N LEU 416 34.683 −6.887 99.722 1.00 35.70 ATOM 1752 CA LEU 416 34.772 −6.480 98.323 1.00 33.93 ATOM 1753 CB LEU 416 34.459 −7.669 97.422 1.00 35.45 ATOM 1754 CG LEU 416 35.609 −8.553 96.946 1.00 36.03 ATOM 1755 CD1 LEU 416 36.708 −8.616 98.004 1.00 35.17 ATOM 1756 CD2 LEU 416 35.046 −9.933 96.610 1.00 35.12 ATOM 1757 C LEU 416 33.831 −5.340 97.949 1.00 31.99 ATOM 1758 O LEU 416 32.631 −5.392 98.222 1.00 31.87 ATOM 1759 N PRO 417 34.366 −4.285 97.319 1.00 29.92 ATOM 1760 CD PRO 417 35.782 −3.965 97.067 1.00 27.19 ATOM 1761 CA PRO 417 33.507 −3.169 96.929 1.00 28.26 ATOM 1762 CB PRO 417 34.509 −2.052 96.705 1.00 24.49 ATOM 1763 CG PRO 417 35.678 −2.776 96.162 1.00 23.69 ATOM 1764 C PRO 417 32.747 −3.548 95.654 1.00 28.94 ATOM 1765 O PRO 417 33.305 −4.215 94.781 1.00 29.04 ATOM 1766 N CYS 418 31.476 −3.166 95.553 1.00 30.16 ATOM 1767 CA CYS 418 30.702 −3.472 94.348 1.00 33.10 ATOM 1768 C CYS 418 29.782 −2.338 93.978 1.00 32.71 ATOM 1769 O CYS 418 29.610 −1.387 94.731 1.00 33.13 ATOM 1770 CB CYS 418 29.808 −4.704 94.510 1.00 35.70 ATOM 1771 SG CYS 418 30.459 −6.095 95.454 1.00 40.35 ATOM 1772 N ARG 419 29.167 −2.479 92.812 1.00 33.12 ATOM 1773 CA ARG 419 28.226 −1.499 92.315 1.00 33.48 ATOM 1774 CB ARG 419 28.937 −0.474 91.418 1.00 35.57 ATOM 1775 CG ARG 419 28.028 0.673 91.009 1.00 42.11 ATOM 1776 CD ARG 419 28.395 1.296 89.654 1.00 47.71 ATOM 1777 NE ARG 419 29.270 2.464 89.754 1.00 50.54 ATOM 1778 CZ ARG 419 30.576 2.412 90.009 1.00 50.62 ATOM 1779 NH1 ARG 419 31.178 1.240 90.189 1.00 50.07 ATOM 1780 NH2 ARG 419 31.279 3.538 90.093 1.00 49.54 ATOM 1781 C ARG 419 27.163 −2.223 91.501 1.00 31.21 ATOM 1782 O ARG 419 27.453 −3.223 90.848 1.00 28.57 ATOM 1783 N ILE 420 25.929 −1.736 91.567 1.00 30.97 ATOM 1784 CA ILE 420 24.845 −2.301 90.759 1.00 31.92 ATOM 1785 CB ILE 420 23.459 −2.255 91.482 1.00 31.58 ATOM 1786 CG2 ILE 420 22.341 −2.527 90.491 1.00 29.56 ATOM 1787 CG1 ILE 420 23.396 −3.308 92.583 1.00 32.48 ATOM 1788 CD1 ILE 420 24.525 −3.201 93.579 1.00 35.47 ATOM 1789 C ILE 420 24.793 −1.378 89.542 1.00 31.56 ATOM 1790 O ILE 420 24.866 −0.161 89.687 1.00 31.84 ATOM 1791 N LYS 421 24.687 −1.938 88.349 1.00 30.80 ATOM 1792 CA LYS 421 24.626 −1.104 87.163 1.00 31.04 ATOM 1793 CB LYS 421 25.808 −1.418 86.259 1.00 32.69 ATOM 1794 CG LYS 421 27.164 −1.194 86.883 1.00 32.84 ATOM 1795 CD LYS 421 28.220 −1.316 85.790 1.00 33.11 ATOM 1796 CE LYS 421 29.583 −0.872 86.271 1.00 32.74 ATOM 1797 NZ LYS 421 30.553 −0.859 85.147 1.00 32.81 ATOM 1798 C LYS 421 23.320 −1.330 86.401 1.00 30.54 ATOM 1799 O LYS 421 22.720 −2.408 86.503 1.00 30.70 ATOM 1800 N GLN 422 22.879 −0.319 85.651 1.00 29.64 ATOM 1801 CA GLN 422 21.652 −0.428 84.859 1.00 30.52 ATOM 1802 CB GLN 422 20.803 0.838 84.969 1.00 30.67 ATOM 1803 CG GLN 422 20.065 0.997 86.279 1.00 32.13 ATOM 1804 CD GLN 422 20.998 1.157 87.466 1.00 33.77 ATOM 1805 OE1 GLN 422 21.823 2.081 87.514 1.00 30.92 ATOM 1806 NE2 GLN 422 20.869 0.255 88.438 1.00 34.85 ATOM 1807 C GLN 422 21.989 −0.669 83.395 1.00 31.34 ATOM 1808 O GLN 422 21.162 −1.159 82.630 1.00 31.50 ATOM 1809 N ILE 423 23.213 −0.321 83.017 1.00 32.09 ATOM 1810 CA ILE 423 23.681 −0.501 81.650 1.00 31.47 ATOM 1811 CB ILE 423 24.220 0.825 81.125 1.00 30.44 ATOM 1812 CG2 ILE 423 24.767 0.662 79.725 1.00 29.43 ATOM 1813 CG1 ILE 423 23.084 1.842 81.151 1.00 29.90 ATOM 1814 CD1 ILE 423 23.454 3.193 80.628 1.00 30.47 ATOM 1815 C ILE 423 24.727 −1.625 81.564 1.00 32.00 ATOM 1816 O ILE 423 25.905 −1.453 81.856 1.00 33.10 ATOM 1817 N ILE 424 24.241 −2.785 81.149 1.00 33.21 ATOM 1818 CA ILE 424 24.995 −4.022 81.017 1.00 33.92 ATOM 1819 CB ILE 424 24.055 −5.212 81.346 1.00 34.97 ATOM 1820 CG2 ILE 424 24.828 −6.487 81.526 1.00 35.83 ATOM 1821 CG1 ILE 424 23.264 −4.900 82.605 1.00 37.56 ATOM 1822 CD1 ILE 424 24.141 −4.483 83.764 1.00 40.47 ATOM 1823 C ILE 424 25.529 −4.276 79.609 1.00 33.77 ATOM 1824 O ILE 424 25.094 −3.670 78.644 1.00 34.71 ATOM 1825 N ASN 425 26.481 −5.194 79.515 1.00 34.13 ATOM 1826 CA ASN 425 27.033 −5.649 78.244 1.00 33.45 ATOM 1827 CB ASN 425 28.559 −5.655 78.279 1.00 33.20 ATOM 1828 CG ASN 425 29.174 −4.556 77.438 1.00 32.66 ATOM 1829 OD1 ASN 425 28.619 −4.149 76.414 1.00 30.45 ATOM 1830 ND2 ASN 425 30.346 −4.087 77.855 1.00 32.53 ATOM 1831 C ASN 425 26.536 −7.081 78.347 1.00 33.79 ATOM 1832 O ASN 425 27.053 −7.826 79.167 1.00 33.77 ATOM 1833 N MET 426 25.539 −7.471 77.554 1.00 35.05 ATOM 1834 CA MET 426 24.974 −8.827 77.653 1.00 36.48 ATOM 1835 CB MET 426 23.788 −8.980 76.698 1.00 37.46 ATOM 1836 CG MET 426 22.690 −7.954 76.921 1.00 42.17 ATOM 1837 SD MET 426 21.033 −8.496 76.443 1.00 47.19 ATOM 1838 CE MET 426 21.110 −8.248 74.701 1.00 47.57 ATOM 1839 C MET 426 25.928 −10.006 77.447 1.00 37.83 ATOM 1840 O MET 426 27.017 −9.867 76.885 1.00 37.54 ATOM 1841 N TRP 427 25.506 −11.176 77.916 1.00 39.73 ATOM 1842 CA TRP 427 26.304 −12.386 77.770 1.00 41.17 ATOM 1843 CB TRP 427 26.323 −13.179 79.085 1.00 42.99 ATOM 1844 CG TRP 427 24.959 −13.556 79.621 1.00 45.82 ATOM 1845 CD2 TRP 427 24.303 −14.822 79.485 1.00 46.80 ATOM 1846 CE2 TRP 427 23.034 −14.709 80.100 1.00 47.00 ATOM 1847 CE3 TRP 427 24.662 −16.044 78.899 1.00 47.97 ATOM 1848 CD1 TRP 427 24.087 −12.748 80.300 1.00 47.03 ATOM 1849 NE1 TRP 427 22.929 −13.434 80.591 1.00 47.49 ATOM 1850 CZ2 TRP 427 22.124 −15.763 80.143 1.00 47.71 ATOM 1851 CZ3 TRP 427 23.756 −17.097 78.944 1.00 48.88 ATOM 1852 CH2 TRP 427 22.500 −16.947 79.562 1.00 49.07 ATOM 1853 C TRP 427 25.812 −13.284 76.632 1.00 41.19 ATOM 1854 O TRP 427 26.607 −13.964 76.000 1.00 41.60 ATOM 1855 N CYS 428 24.509 −13.272 76.363 1.00 42.00 ATOM 1856 CA CYS 428 23.922 −14.101 75.308 1.00 44.36 ATOM 1857 C CYS 428 24.410 −13.749 73.917 1.00 44.00 ATOM 1858 O CYS 428 24.887 −14.616 73.176 1.00 44.48 ATOM 1859 CB CYS 428 22.394 −14.023 75.381 1.00 47.62 ATOM 1860 SG CYS 428 21.874 −14.854 76.914 1.00 57.16 ATOM 1861 N LYS 429 24.290 −12.479 73.557 1.00 43.21 ATOM 1862 CA LYS 429 24.750 −12.015 72.263 1.00 41.60 ATOM 1863 CB LYS 429 23.569 −11.882 71.307 1.00 42.35 ATOM 1864 CG LYS 429 22.384 −11.156 71.883 1.00 43.72 ATOM 1865 CD LYS 429 21.248 −11.148 70.901 1.00 45.78 ATOM 1866 CE LYS 429 20.053 −10.418 71.475 1.00 47.56 ATOM 1867 NZ LYS 429 18.901 −10.405 70.517 1.00 50.92 ATOM 1868 C LYS 429 25.423 −10.673 72.495 1.00 40.41 ATOM 1869 O LYS 429 25.256 −10.073 73.553 1.00 40.49 ATOM 1870 N VAL 430 26.193 −10.213 71.521 1.00 39.52 ATOM 1871 CA VAL 430 26.879 −8.944 71.645 1.00 39.11 ATOM 1872 CB VAL 430 27.937 −8.791 70.532 1.00 37.84 ATOM 1873 CG1 VAL 430 28.489 −7.380 70.507 1.00 39.67 ATOM 1874 CG2 VAL 430 29.073 −9.761 70.743 1.00 35.62 ATOM 1875 C VAL 430 25.914 −7.764 71.573 1.00 40.33 ATOM 1876 O VAL 430 25.783 −7.136 70.539 1.00 42.24 ATOM 1877 N CYS 431 25.211 −7.470 72.657 1.00 41.16 ATOM 1878 CA CYS 431 24.291 −6.326 72.682 1.00 43.40 ATOM 1879 C CYS 431 24.499 −5.530 73.970 1.00 42.17 ATOM 1880 O CYS 431 25.000 −6.062 74.964 1.00 43.09 ATOM 1881 CB CYS 431 22.835 −6.780 72.668 1.00 48.10 ATOM 1882 SG CYS 431 22.257 −7.836 71.299 1.00 60.95 ATOM 1883 N LYS 432 24.119 −4.257 73.960 1.00 38.87 ATOM 1884 CA LYS 432 24.226 −3.454 75.164 1.00 36.15 ATOM 1885 CB LYS 432 24.860 −2.104 74.846 1.00 35.67 ATOM 1886 CG LYS 432 25.975 −1.723 75.807 1.00 37.19 ATOM 1887 CD LYS 432 26.857 −0.647 75.192 1.00 39.70 ATOM 1888 CE LYS 432 28.075 −0.335 76.058 1.00 42.82 ATOM 1889 NZ LYS 432 28.992 −1.509 76.255 1.00 42.87 ATOM 1890 C LYS 432 22.794 −3.297 75.680 1.00 35.02 ATOM 1891 O LYS 432 21.888 −3.024 74.909 1.00 35.60 ATOM 1892 N ALA 433 22.574 −3.497 76.972 1.00 33.36 ATOM 1893 CA ALA 433 21.226 −3.385 77.500 1.00 33.09 ATOM 1894 CB ALA 433 20.714 −4.753 77.881 1.00 33.61 ATOM 1895 C ALA 433 21.156 −2.460 78.696 1.00 34.02 ATOM 1896 O ALA 433 22.129 −2.309 79.420 1.00 35.31 ATOM 1897 N MET 434 20.006 −1.830 78.908 1.00 34.39 ATOM 1898 CA MET 434 19.853 −0.927 80.043 1.00 34.19 ATOM 1899 CB MET 434 19.688 0.522 79.577 1.00 34.29 ATOM 1900 CG MET 434 19.537 1.519 80.722 1.00 35.19 ATOM 1901 SD MET 434 18.772 3.088 80.230 1.00 38.57 ATOM 1902 CE MET 434 17.017 2.778 80.598 1.00 37.43 ATOM 1903 C MET 434 18.626 −1.328 80.841 1.00 34.05 ATOM 1904 O MET 434 17.522 −1.387 80.307 1.00 35.74 ATOM 1905 N TYR 435 18.817 −1.602 82.123 1.00 32.51 ATOM 1906 CA TYR 435 17.709 −1.984 82.973 1.00 30.96 ATOM 1907 CB TYR 435 18.106 −3.184 83.822 1.00 29.29 ATOM 1908 CG TYR 435 18.339 −4.417 82.992 1.00 25.84 ATOM 1909 CD1 TYR 435 19.560 −4.636 82.365 1.00 25.45 ATOM 1910 CE1 TYR 435 19.745 −5.711 81.524 1.00 24.61 ATOM 1911 CD2 TYR 435 17.311 −5.314 82.760 1.00 23.29 ATOM 1912 CE2 TYR 435 17.482 −6.382 81.924 1.00 24.52 ATOM 1913 CZ TYR 435 18.699 −6.581 81.305 1.00 24.68 ATOM 1914 OH TYR 435 18.847 −7.648 80.450 1.00 26.95 ATOM 1915 C TYR 435 17.313 −0.828 83.859 1.00 32.33 ATOM 1916 O TYR 435 18.001 0.195 83.892 1.00 33.56 ATOM 1917 N ALA 436 16.203 −0.984 84.576 1.00 32.62 ATOM 1918 CA ALA 436 15.736 0.067 85.473 1.00 33.64 ATOM 1919 CB ALA 436 14.236 −0.064 85.698 1.00 31.13 ATOM 1920 C ALA 436 16.494 −0.003 86.813 1.00 35.55 ATOM 1921 O ALA 436 17.025 −1.058 87.199 1.00 36.85 ATOM 1922 N PRO 437 16.580 1.132 87.527 1.00 35.03 ATOM 1923 CD PRO 437 16.171 2.473 87.084 1.00 34.29 ATOM 1924 CA PRO 437 17.270 1.198 88.817 1.00 34.44 ATOM 1925 CB PRO 437 17.150 2.665 89.182 1.00 35.20 ATOM 1926 CG PRO 437 17.130 3.339 87.833 1.00 35.19 ATOM 1927 C PRO 437 16.572 0.287 89.825 1.00 35.06 ATOM 1928 O PRO 437 15.471 −0.200 89.562 1.00 36.23 ATOM 1929 N PRO 438 17.188 0.051 90.994 1.00 33.79 ATOM 1930 CD PRO 438 18.576 0.364 91.356 1.00 33.35 ATOM 1931 CA PRO 438 16.587 −0.820 92.008 1.00 34.09 ATOM 1932 CB PRO 438 17.729 −1.028 92.994 1.00 33.97 ATOM 1933 CG PRO 438 18.947 −0.849 92.167 1.00 33.01 ATOM 1934 C PRO 438 15.343 −0.263 92.694 1.00 35.40 ATOM 1935 O PRO 438 15.116 0.945 92.706 1.00 35.71 ATOM 1936 N ILE 439 14.524 −1.151 93.253 1.00 36.30 ATOM 1937 CA ILE 439 13.333 −0.707 93.962 1.00 36.39 ATOM 1938 CB ILE 439 12.008 −1.142 93.261 1.00 34.37 ATOM 1939 CG2 ILE 439 12.003 −0.699 91.836 1.00 34.23 ATOM 1940 CG1 ILE 439 11.845 −2.653 93.288 1.00 35.39 ATOM 1941 CD1 ILE 439 10.469 −3.098 92.843 1.00 34.29 ATOM 1942 C ILE 439 13.367 −1.242 95.393 1.00 37.68 ATOM 1943 O ILE 439 12.507 −0.911 96.204 1.00 39.13 ATOM 1944 N SER 440 14.364 −2.062 95.705 1.00 37.37 ATOM 1945 CA SER 440 14.491 −2.584 97.057 1.00 39.32 ATOM 1946 CB SER 440 14.604 −4.104 97.054 1.00 40.44 ATOM 1947 OG SER 440 14.933 −4.568 98.362 1.00 40.66 ATOM 1948 C SER 440 15.707 −2.011 97.774 1.00 40.33 ATOM 1949 O SER 440 16.679 −1.597 97.135 1.00 41.36 ATOM 1950 N GLY 441 15.646 −1.994 99.102 1.00 40.54 ATOM 1951 CA GLY 441 16.752 −1.482 99.890 1.00 42.17 ATOM 1952 C GLY 441 17.425 −2.604 100.659 1.00 43.06 ATOM 1953 O GLY 441 18.367 −2.392 101.437 1.00 42.78 ATOM 1954 N GLN 442 16.920 −3.811 100.439 1.00 43.64 ATOM 1955 CA GLN 442 17.445 −4.997 101.085 1.00 44.67 ATOM 1956 CB GLN 442 16.475 −5.475 102.175 1.00 45.38 ATOM 1957 CG GLN 442 16.864 −5.030 103.587 1.00 47.90 ATOM 1958 CD GLN 442 15.750 −5.219 104.621 1.00 49.44 ATOM 1959 OE1 GLN 442 14.751 −4.495 104.599 1.00 50.66 ATOM 1960 NE2 GLN 442 15.921 −6.190 105.530 1.00 47.39 ATOM 1961 C GLN 442 17.679 −6.080 100.035 1.00 44.84 ATOM 1962 O GLN 442 16.909 −7.032 99.904 1.00 44.57 ATOM 1963 N ILE 443 18.755 −5.908 99.278 1.00 45.49 ATOM 1964 CA ILE 443 19.132 −6.851 98.236 1.00 46.47 ATOM 1965 CB ILE 443 19.492 −6.092 96.941 1.00 45.56 ATOM 1966 CG2 ILE 443 20.064 −7.039 95.908 1.00 44.09 ATOM 1967 CG1 ILE 443 18.238 −5.392 96.411 1.00 45.07 ATOM 1968 CD1 ILE 443 18.433 −4.604 95.153 1.00 44.19 ATOM 1969 C ILE 443 20.328 −7.651 98.744 1.00 47.21 ATOM 1970 O ILE 443 21.449 −7.142 98.782 1.00 47.84 ATOM 1971 N ARG 444 20.087 −8.899 99.135 1.00 47.05 ATOM 1972 CA ARG 444 21.150 −9.732 99.681 1.00 48.36 ATOM 1973 CB ARG 444 20.856 −10.036 101.152 1.00 50.00 ATOM 1974 CG ARG 444 20.436 −8.837 101.994 1.00 52.86 ATOM 1975 CD ARG 444 21.439 −8.535 103.105 1.00 55.04 ATOM 1976 NE ARG 444 20.951 −7.500 104.017 1.00 59.88 ATOM 1977 CZ ARG 444 20.629 −6.255 103.659 1.00 61.86 ATOM 1978 NH1 ARG 444 20.193 −5.391 104.570 1.00 62.57 ATOM 1979 NH2 ARG 444 20.741 −5.862 102.395 1.00 62.40 ATOM 1980 C ARG 444 21.361 −11.052 98.948 1.00 48.73 ATOM 1981 O ARG 444 20.405 −11.671 98.481 1.00 49.67 ATOM 1982 N CYS 445 22.619 −11.479 98.849 1.00 48.63 ATOM 1983 CA CYS 445 22.956 −12.749 98.212 1.00 47.62 ATOM 1984 C CYS 445 24.029 −13.502 98.946 1.00 45.78 ATOM 1985 O CYS 445 25.207 −13.129 98.931 1.00 45.76 ATOM 1986 CB CYS 445 23.392 −12.574 96.762 1.00 50.80 ATOM 1987 SG CYS 445 21.966 −12.871 95.692 1.00 57.24 ATOM 1988 N SER 446 23.595 −14.574 99.589 1.00 42.24 ATOM 1989 CA SER 446 24.471 −15.438 100.339 1.00 39.56 ATOM 1990 CB SER 446 23.764 −15.885 101.600 1.00 40.45 ATOM 1991 OG SER 446 22.870 −14.868 102.024 1.00 43.28 ATOM 1992 C SER 446 24.667 −16.613 99.417 1.00 37.50 ATOM 1993 O SER 446 23.767 −17.424 99.252 1.00 37.85 ATOM 1994 N SER 447 25.833 −16.693 98.795 1.00 34.81 ATOM 1995 CA SER 447 26.095 −17.780 97.881 1.00 33.45 ATOM 1996 CB SER 447 26.331 −17.227 96.485 1.00 34.56 ATOM 1997 OG SER 447 25.323 −16.307 96.128 1.00 36.68 ATOM 1998 C SER 447 27.300 −18.588 98.300 1.00 32.91 ATOM 1999 O SER 447 28.088 −18.178 99.151 1.00 33.16 ATOM 2000 N ASN 448 27.432 −19.755 97.697 1.00 32.65 ATOM 2001 CA ASN 448 28.561 −20.620 97.970 1.00 33.16 ATOM 2002 CB ASN 448 28.088 −22.019 98.361 1.00 35.97 ATOM 2003 CG ASN 448 27.950 −22.184 99.852 1.00 41.24 ATOM 2004 OD1 ASN 448 28.938 −22.162 100.574 1.00 42.95 ATOM 2005 ND2 ASN 448 26.727 −22.357 100.331 1.00 46.28 ATOM 2006 C ASN 448 29.444 −20.706 96.731 1.00 31.71 ATOM 2007 O ASN 448 29.005 −21.162 95.668 1.00 30.58 ATOM 2008 N ILE 449 30.675 −20.222 96.862 1.00 29.84 ATOM 2009 CA ILE 449 31.645 −20.292 95.772 1.00 27.37 ATOM 2010 CB ILE 449 32.980 −19.595 96.137 1.00 25.12 ATOM 2011 CG2 ILE 449 34.005 −19.817 95.040 1.00 24.87 ATOM 2012 CG1 ILE 449 32.766 −18.110 96.374 1.00 22.91 ATOM 2013 CD1 ILE 449 34.006 −17.435 96.882 1.00 20.04 ATOM 2014 C ILE 449 31.929 −21.784 95.734 1.00 27.61 ATOM 2015 O ILE 449 32.203 −22.373 96.785 1.00 29.12 ATOM 2016 N THR 450 31.854 −22.409 94.567 1.00 25.09 ATOM 2017 CA THR 450 32.134 −23.836 94.501 1.00 24.31 ATOM 2018 CB THR 450 30.832 −24.667 94.295 1.00 24.01 ATOM 2019 OG1 THR 450 30.135 −24.223 93.121 1.00 23.07 ATOM 2020 CG2 THR 450 29.927 −24.523 95.489 1.00 22.78 ATOM 2021 C THR 450 33.108 −24.109 93.368 1.00 24.60 ATOM 2022 O THR 450 33.469 −25.248 93.088 1.00 23.80 ATOM 2023 N GLY 451 33.542 −23.042 92.718 1.00 25.04 ATOM 2024 CA GLY 451 34.470 −23.200 91.620 1.00 26.73 ATOM 2025 C GLY 451 34.924 −21.855 91.118 1.00 26.65 ATOM 2026 O GLY 451 34.370 −20.828 91.505 1.00 27.30 ATOM 2027 N LEU 452 35.945 −21.851 90.273 1.00 26.29 ATOM 2028 CA LEU 452 36.439 −20.592 89.739 1.00 27.72 ATOM 2029 CB LEU 452 37.798 −20.211 90.351 1.00 25.03 ATOM 2030 CG LEU 452 37.865 −19.937 91.850 1.00 23.22 ATOM 2031 CD1 LEU 452 37.792 −21.248 92.592 1.00 22.91 ATOM 2032 CD2 LEU 452 39.150 −19.225 92.198 1.00 22.12 ATOM 2033 C LEU 452 36.602 −20.720 88.249 1.00 27.91 ATOM 2034 O LEU 452 36.381 −21.784 87.678 1.00 30.44 ATOM 2035 N LEU 453 36.983 −19.620 87.626 1.00 25.60 ATOM 2036 CA LEU 453 37.223 −19.605 86.211 1.00 24.90 ATOM 2037 CB LEU 453 36.071 −18.936 85.473 1.00 21.07 ATOM 2038 CG LEU 453 34.724 −19.652 85.532 1.00 16.96 ATOM 2039 CD1 LEU 453 33.754 −18.930 84.649 1.00 17.51 ATOM 2040 CD2 LEU 453 34.850 −21.061 85.077 1.00 13.58 ATOM 2041 C LEU 453 38.485 −18.790 86.124 1.00 27.06 ATOM 2042 O LEU 453 38.458 −17.568 86.262 1.00 28.02 ATOM 2043 N LEU 454 39.602 −19.480 85.936 1.00 28.63 ATOM 2044 CA LEU 454 40.889 −18.809 85.862 1.00 30.83 ATOM 2045 CB LEU 454 41.898 −19.483 86.789 1.00 29.19 ATOM 2046 CG LEU 454 41.646 −19.667 88.277 1.00 28.21 ATOM 2047 CD1 LEU 454 42.802 −20.460 88.863 1.00 28.15 ATOM 2048 CD2 LEU 454 41.527 −18.331 88.961 1.00 28.25 ATOM 2049 C LEU 454 41.474 −18.815 84.465 1.00 32.86 ATOM 2050 O LEU 454 41.103 −19.631 83.622 1.00 33.87 ATOM 2051 N THR 455 42.415 −17.904 84.248 1.00 34.41 ATOM 2052 CA THR 455 43.123 −17.791 82.984 1.00 37.13 ATOM 2053 CB THR 455 42.759 −16.519 82.250 1.00 38.41 ATOM 2054 OG1 THR 455 41.340 −16.467 82.075 1.00 41.71 ATOM 2055 CG2 THR 455 43.438 −16.491 80.893 1.00 38.74 ATOM 2056 C THR 455 44.591 −17.716 83.344 1.00 38.29 ATOM 2057 O THR 455 44.943 −17.138 84.367 1.00 38.34 ATOM 2058 N ARG 456 45.450 −18.289 82.508 1.00 39.99 ATOM 2059 CA ARG 456 46.881 −18.277 82.783 1.00 41.61 ATOM 2060 CB ARG 456 47.424 −19.698 82.719 1.00 42.00 ATOM 2061 CG ARG 456 48.889 −19.811 83.063 1.00 44.96 ATOM 2062 CD ARG 456 49.323 −21.250 82.973 1.00 47.06 ATOM 2063 NE ARG 456 49.147 −21.774 81.621 1.00 49.39 ATOM 2064 CZ ARG 456 50.117 −21.842 80.714 1.00 50.82 ATOM 2065 NH1 ARG 456 49.857 −22.331 79.506 1.00 52.13 ATOM 2066 NH2 ARG 456 51.348 −21.439 81.019 1.00 49.94 ATOM 2067 C ARG 456 47.664 −17.389 81.825 1.00 42.48 ATOM 2068 O ARG 456 47.665 −17.626 80.624 1.00 41.96 ATOM 2069 N ASP 457 48.333 −16.371 82.362 1.00 44.50 ATOM 2070 CA ASP 457 49.124 −15.451 81.541 1.00 46.62 ATOM 2071 CB ASP 457 49.969 −14.515 82.414 1.00 45.79 ATOM 2072 CG ASP 457 49.169 −13.352 82.978 1.00 46.16 ATOM 2073 OD1 ASP 457 49.798 −12.434 83.549 1.00 44.86 ATOM 2074 OD2 ASP 457 47.921 −13.355 82.853 1.00 44.91 ATOM 2075 C ASP 457 50.051 −16.199 80.597 1.00 48.50 ATOM 2076 O ASP 457 49.941 −16.088 79.378 1.00 48.45 ATOM 2077 N GLY 458 50.975 −16.959 81.168 1.00 51.31 ATOM 2078 CA GLY 458 51.898 −17.712 80.346 1.00 54.51 ATOM 2079 C GLY 458 52.751 −16.795 79.499 1.00 57.29 ATOM 2080 O GLY 458 53.043 −15.659 79.886 1.00 56.35 ATOM 2081 N GLY 459 53.145 −17.288 78.332 1.00 60.01 ATOM 2082 CA GLY 459 53.980 −16.494 77.454 1.00 63.76 ATOM 2083 C GLY 459 55.443 −16.727 77.769 1.00 66.68 ATOM 2084 O GLY 459 55.830 −16.889 78.932 1.00 66.19 ATOM 2085 N ASN 460 56.254 −16.735 76.716 1.00 69.80 ATOM 2086 CA ASN 460 57.694 −16.954 76.813 1.00 73.18 ATOM 2087 CB ASN 460 58.357 −16.575 75.486 1.00 73.04 ATOM 2088 CG ASN 460 57.866 −17.426 74.325 1.00 73.09 ATOM 2089 OD1 ASN 460 56.884 −18.161 74.450 1.00 73.18 ATOM 2090 ND2 ASN 460 58.543 −17.323 73.186 1.00 72.64 ATOM 2091 C ASN 460 58.409 −16.242 77.965 1.00 75.44 ATOM 2092 O ASN 460 58.412 −15.010 78.062 1.00 75.19 ATOM 2093 N SER 461 59.021 −17.051 78.828 1.00 77.97 ATOM 2094 CA SER 461 59.771 −16.582 79.987 1.00 80.75 ATOM 2095 CB SER 461 58.858 −15.820 80.955 1.00 80.97 ATOM 2096 OG SER 461 59.608 −15.227 82.007 1.00 81.02 ATOM 2097 C SER 461 60.368 −17.804 80.689 1.00 82.74 ATOM 2098 O SER 461 59.649 −18.579 81.332 1.00 82.67 ATOM 2099 N ASN 462 61.682 −17.979 80.545 1.00 84.51 ATOM 2100 CA ASN 462 62.399 −19.101 81.160 1.00 85.75 ATOM 2101 CB ASN 462 63.877 −19.043 80.770 1.00 86.14 ATOM 2102 CG ASN 462 64.408 −17.626 80.735 1.00 86.77 ATOM 2103 OD1 ASN 462 64.320 −16.891 81.723 1.00 87.52 ATOM 2104 ND2 ASN 462 64.963 −17.230 79.594 1.00 86.09 ATOM 2105 C ASN 462 62.248 −19.078 82.681 1.00 85.99 ATOM 2106 O ASN 462 62.664 −20.014 83.377 1.00 86.05 ATOM 2107 N ASN 463 61.648 −17.992 83.172 1.00 85.36 ATOM 2108 CA ASN 463 61.379 −17.775 84.591 1.00 84.11 ATOM 2109 CB ASN 463 60.737 −16.395 84.774 1.00 86.07 ATOM 2110 CG ASN 463 60.656 −15.967 86.227 1.00 88.02 ATOM 2111 OD1 ASN 463 60.296 −16.757 87.101 1.00 90.17 ATOM 2112 ND2 ASN 463 60.976 −14.703 86.490 1.00 88.10 ATOM 2113 C ASN 463 60.392 −18.861 85.012 1.00 82.29 ATOM 2114 O ASN 463 59.372 −19.058 84.351 1.00 82.70 ATOM 2115 N GLU 464 60.684 −19.569 86.098 1.00 79.57 ATOM 2116 CA GLU 464 59.788 −20.631 86.542 1.00 76.54 ATOM 2117 CB GLU 464 60.598 −21.833 87.058 1.00 79.45 ATOM 2118 CG GLU 464 61.323 −22.608 85.943 1.00 82.50 ATOM 2119 CD GLU 464 62.120 −23.814 86.448 1.00 85.16 ATOM 2120 OE1 GLU 464 62.812 −24.457 85.620 1.00 85.88 ATOM 2121 OE2 GLU 464 62.055 −24.121 87.663 1.00 85.82 ATOM 2122 C GLU 464 58.765 −20.185 87.583 1.00 72.60 ATOM 2123 O GLU 464 58.986 −20.303 88.788 1.00 71.55 ATOM 2124 N SER 465 57.639 −19.677 87.081 1.00 68.78 ATOM 2125 CA SER 465 56.516 −19.200 87.893 1.00 64.10 ATOM 2126 CB SER 465 56.918 −17.974 88.715 1.00 63.31 ATOM 2127 OG SER 465 57.130 −16.853 87.880 1.00 60.85 ATOM 2128 C SER 465 55.356 −18.818 86.968 1.00 60.87 ATOM 2129 O SER 465 55.526 −18.016 86.049 1.00 59.72 ATOM 2130 N GLU 466 54.184 −19.397 87.215 1.00 57.26 ATOM 2131 CA GLU 466 52.994 −19.126 86.410 1.00 53.95 ATOM 2132 CB GLU 466 52.200 −20.413 86.211 1.00 54.65 ATOM 2133 CG GLU 466 52.956 −21.470 85.438 1.00 56.85 ATOM 2134 CD GLU 466 53.221 −21.049 84.011 1.00 57.73 ATOM 2135 OE1 GLU 466 54.153 −21.608 83.395 1.00 58.80 ATOM 2136 OE2 GLU 466 52.492 −20.165 83.506 1.00 57.31 ATOM 2137 C GLU 466 52.110 −18.087 87.080 1.00 51.49 ATOM 2138 O GLU 466 52.057 −18.015 88.306 1.00 51.94 ATOM 2139 N ILE 467 51.419 −17.276 86.283 1.00 47.68 ATOM 2140 CA ILE 467 50.543 −16.254 86.850 1.00 44.16 ATOM 2141 CB ILE 467 50.903 −14.837 86.354 1.00 42.54 ATOM 2142 CG2 ILE 467 50.189 −13.805 87.209 1.00 41.04 ATOM 2143 CG1 ILE 467 52.410 −14.601 86.454 1.00 41.74 ATOM 2144 CD1 ILE 467 52.829 −13.208 86.044 1.00 40.72 ATOM 2145 C ILE 467 49.100 −16.539 86.466 1.00 42.71 ATOM 2146 O ILE 467 48.817 −16.864 85.315 1.00 43.08 ATOM 2147 N PHE 468 48.187 −16.421 87.423 1.00 39.98 ATOM 2148 CA PHE 468 46.793 −16.684 87.129 1.00 38.70 ATOM 2149 CB PHE 468 46.347 −17.953 87.827 1.00 39.01 ATOM 2150 CG PHE 468 47.216 −19.127 87.541 1.00 40.09 ATOM 2151 CD1 PHE 468 48.465 −19.243 88.145 1.00 40.16 ATOM 2152 CD2 PHE 468 46.789 −20.127 86.670 1.00 41.47 ATOM 2153 CE1 PHE 468 49.280 −20.334 87.891 1.00 40.98 ATOM 2154 CE2 PHE 468 47.596 −21.229 86.404 1.00 42.44 ATOM 2155 CZ PHE 468 48.847 −21.333 87.018 1.00 42.97 ATOM 2156 C PHE 468 45.863 −15.552 87.515 1.00 38.30 ATOM 2157 O PHE 468 46.022 −14.928 88.563 1.00 39.47 ATOM 2158 N ARG 469 44.876 −15.305 86.664 1.00 36.77 ATOM 2159 CA ARG 469 43.912 −14.250 86.897 1.00 35.74 ATOM 2160 CB ARG 469 44.139 −13.121 85.907 1.00 34.66 ATOM 2161 CG ARG 469 45.560 −12.642 85.831 1.00 33.62 ATOM 2162 CD ARG 469 45.735 −11.760 84.620 1.00 33.99 ATOM 2163 NE ARG 469 47.111 −11.330 84.426 1.00 32.62 ATOM 2164 CZ ARG 469 47.721 −10.426 85.179 1.00 32.46 ATOM 2165 NH1 ARG 469 47.083 −9.851 86.182 1.00 32.30 ATOM 2166 NH2 ARG 469 48.968 −10.089 84.918 1.00 33.90 ATOM 2167 C ARG 469 42.522 −14.811 86.690 1.00 35.90 ATOM 2168 O ARG 469 42.344 −15.782 85.968 1.00 37.30 ATOM 2169 N PRO 470 41.512 −14.196 87.316 1.00 36.11 ATOM 2170 CD PRO 470 41.626 −13.004 88.173 1.00 37.74 ATOM 2171 CA PRO 470 40.117 −14.628 87.205 1.00 35.55 ATOM 2172 CB PRO 470 39.425 −13.835 88.306 1.00 37.42 ATOM 2173 CG PRO 470 40.181 −12.546 88.299 1.00 37.79 ATOM 2174 C PRO 470 39.572 −14.304 85.826 1.00 34.84 ATOM 2175 O PRO 470 39.664 −13.163 85.350 1.00 32.79 ATOM 2176 N GLY 471 39.009 −15.318 85.182 1.00 34.39 ATOM 2177 CA GLY 471 38.481 −15.126 83.849 1.00 34.12 ATOM 2178 C GLY 471 37.014 −15.447 83.762 1.00 33.66 ATOM 2179 O GLY 471 36.250 −15.157 84.681 1.00 32.21 ATOM 2180 N GLY 472 36.630 −16.054 82.646 1.00 34.79 ATOM 2181 CA GLY 472 35.242 −16.408 82.433 1.00 36.19 ATOM 2182 C GLY 472 34.526 −15.361 81.600 1.00 37.07 ATOM 2183 O GLY 472 35.141 −14.417 81.090 1.00 37.63 ATOM 2184 N GLY 473 33.218 −15.516 81.471 1.00 36.43 ATOM 2185 CA GLY 473 32.451 −14.578 80.687 1.00 36.25 ATOM 2186 C GLY 473 31.703 −15.393 79.669 1.00 37.28 ATOM 2187 O GLY 473 30.653 −14.982 79.179 1.00 37.79 ATOM 2188 N ASP 474 32.253 −16.562 79.351 1.00 37.46 ATOM 2189 CA ASP 474 31.620 −17.455 78.396 1.00 38.13 ATOM 2190 CB ASP 474 32.666 −18.142 77.528 1.00 39.46 ATOM 2191 CG ASP 474 32.042 −18.956 76.420 1.00 41.78 ATOM 2192 OD1 ASP 474 30.863 −19.345 76.567 1.00 41.80 ATOM 2193 OD2 ASP 474 32.726 −19.215 75.408 1.00 43.88 ATOM 2194 C ASP 474 30.842 −18.501 79.179 1.00 37.74 ATOM 2195 O ASP 474 31.350 −19.584 79.445 1.00 38.81 ATOM 2196 N MET 475 29.609 −18.166 79.543 1.00 37.28 ATOM 2197 CA MET 475 28.741 −19.049 80.318 1.00 36.81 ATOM 2198 CB MET 475 27.297 −18.559 80.213 1.00 36.74 ATOM 2199 CG MET 475 26.718 −18.082 81.529 1.00 37.69 ATOM 2200 SD MET 475 27.926 −17.234 82.557 1.00 38.71 ATOM 2201 CE MET 475 28.119 −15.706 81.638 1.00 38.89 ATOM 2202 C MET 475 28.814 −20.542 79.979 1.00 37.19 ATOM 2203 O MET 475 28.382 −21.382 80.773 1.00 37.30 ATOM 2204 N ARG 476 29.353 −20.878 78.809 1.00 36.64 ATOM 2205 CA ARG 476 29.484 −22.273 78.420 1.00 34.96 ATOM 2206 CB ARG 476 29.919 −22.392 76.973 1.00 37.33 ATOM 2207 CG ARG 476 28.879 −21.935 75.991 1.00 39.91 ATOM 2208 CD ARG 476 29.264 −22.348 74.595 1.00 43.35 ATOM 2209 NE ARG 476 28.644 −21.475 73.610 1.00 48.16 ATOM 2210 CZ ARG 476 29.072 −20.246 73.339 1.00 50.83 ATOM 2211 NH1 ARG 476 30.130 −19.751 73.978 1.00 50.44 ATOM 2212 NH2 ARG 476 28.434 −19.508 72.438 1.00 52.09 ATOM 2213 C ARG 476 30.505 −22.950 79.309 1.00 34.15 ATOM 2214 O ARG 476 30.466 −24.155 79.495 1.00 33.39 ATOM 2215 N ASP 477 31.437 −22.175 79.846 1.00 33.97 ATOM 2216 CA ASP 477 32.428 −22.731 80.748 1.00 34.21 ATOM 2217 CB ASP 477 33.497 −21.702 81.091 1.00 34.12 ATOM 2218 CG ASP 477 34.475 −21.478 79.971 1.00 35.39 ATOM 2219 OD1 ASP 477 34.800 −22.449 79.256 1.00 36.22 ATOM 2220 OD2 ASP 477 34.937 −20.326 79.823 1.00 37.07 ATOM 2221 C ASP 477 31.696 −23.120 82.030 1.00 35.79 ATOM 2222 O ASP 477 31.977 −24.157 82.640 1.00 36.61 ATOM 2223 N ASN 478 30.753 −22.278 82.440 1.00 35.81 ATOM 2224 CA ASN 478 29.992 −22.539 83.647 1.00 35.64 ATOM 2225 CB ASN 478 29.160 −21.315 84.029 1.00 37.76 ATOM 2226 CG ASN 478 29.987 −20.040 84.081 1.00 39.41 ATOM 2227 OD1 ASN 478 29.613 −19.070 84.748 1.00 40.06 ATOM 2228 ND2 ASN 478 31.108 −20.029 83.363 1.00 37.85 ATOM 2229 C ASN 478 29.096 −23.756 83.478 1.00 34.88 ATOM 2230 O ASN 478 28.958 −24.550 84.389 1.00 34.09 ATOM 2231 N TRP 479 28.479 −23.906 82.316 1.00 34.86 ATOM 2232 CA TRP 479 27.641 −25.070 82.078 1.00 36.03 ATOM 2233 CB TRP 479 26.892 −24.932 80.760 1.00 37.78 ATOM 2234 CG TRP 479 26.218 −23.624 80.555 1.00 40.26 ATOM 2235 CD2 TRP 479 25.541 −22.847 81.536 1.00 40.78 ATOM 2236 CE2 TRP 479 25.028 −21.702 80.883 1.00 41.01 ATOM 2237 CE3 TRP 479 25.314 −23.002 82.904 1.00 41.79 ATOM 2238 CD1 TRP 479 26.095 −22.943 79.374 1.00 41.62 ATOM 2239 NE1 TRP 479 25.380 −21.787 79.562 1.00 41.25 ATOM 2240 CZ2 TRP 479 24.307 −20.719 81.552 1.00 40.72 ATOM 2241 CZ3 TRP 479 24.595 −22.023 83.569 1.00 43.55 ATOM 2242 CH2 TRP 479 24.099 −20.894 82.889 1.00 42.51 ATOM 2243 C TRP 479 28.576 −26.270 81.972 1.00 35.96 ATOM 2244 O TRP 479 28.297 −27.346 82.476 1.00 37.65 ATOM 2245 N ARG 480 29.700 −26.070 81.304 1.00 36.48 ATOM 2246 CA ARG 480 30.685 −27.126 81.108 1.00 37.20 ATOM 2247 CB ARG 480 31.863 −26.576 80.284 1.00 39.00 ATOM 2248 CG ARG 480 32.614 −27.615 79.462 1.00 40.70 ATOM 2249 CD ARG 480 33.888 −27.058 78.807 1.00 42.07 ATOM 2250 NE ARG 480 33.624 −25.883 77.995 1.00 41.84 ATOM 2251 CZ ARG 480 32.745 −25.850 77.002 1.00 41.61 ATOM 2252 NH1 ARG 480 32.044 −26.937 76.691 1.00 41.31 ATOM 2253 NH2 ARG 480 32.552 −24.720 76.337 1.00 41.06 ATOM 2254 C ARG 480 31.202 −27.706 82.428 1.00 36.72 ATOM 2255 O ARG 480 31.560 −28.869 82.495 1.00 37.82 ATOM 2256 N SER 481 31.236 −26.899 83.479 1.00 36.72 ATOM 2257 CA SER 481 31.738 −27.367 84.765 1.00 37.00 ATOM 2258 CB SER 481 32.088 −26.182 85.645 1.00 36.50 ATOM 2259 OG SER 481 30.897 −25.619 86.144 1.00 33.89 ATOM 2260 C SER 481 30.742 −28.243 85.516 1.00 37.55 ATOM 2261 O SER 481 31.024 −28.717 86.616 1.00 36.47 ATOM 2262 N GLU 482 29.575 −28.453 84.933 1.00 38.59 ATOM 2263 CA GLU 482 28.572 −29.269 85.583 1.00 40.68 ATOM 2264 CB GLU 482 27.350 −28.418 85.922 1.00 42.64 ATOM 2265 CG GLU 482 27.521 −27.504 87.131 1.00 44.81 ATOM 2266 CD GLU 482 26.957 −28.100 88.412 1.00 46.18 ATOM 2267 OE1 GLU 482 25.726 −28.318 88.481 1.00 47.32 ATOM 2268 OE2 GLU 482 27.744 −28.348 89.353 1.00 46.06 ATOM 2269 C GLU 482 28.163 −30.428 84.697 1.00 41.36 ATOM 2270 O GLU 482 27.733 −31.472 85.188 1.00 43.64 ATOM 2271 N LEU 483 28.304 −30.255 83.391 1.00 40.45 ATOM 2272 CA LEU 483 27.919 −31.303 82.459 1.00 40.92 ATOM 2273 CB LEU 483 27.182 −30.673 81.283 1.00 40.20 ATOM 2274 CG LEU 483 25.928 −29.921 81.723 1.00 40.80 ATOM 2275 CD1 LEU 483 25.420 −29.072 80.587 1.00 41.63 ATOM 2276 CD2 LEU 483 24.874 −30.909 82.175 1.00 41.17 ATOM 2277 C LEU 483 29.096 −32.132 81.951 1.00 41.69 ATOM 2278 O LEU 483 28.931 −33.000 81.092 1.00 41.28 ATOM 2279 N TYR 484 30.282 −31.880 82.492 1.00 41.67 ATOM 2280 CA TYR 484 31.463 −32.598 82.050 1.00 42.77 ATOM 2281 CB TYR 484 32.684 −32.103 82.830 1.00 42.89 ATOM 2282 CG TYR 484 32.695 −32.515 84.277 1.00 43.93 ATOM 2283 CD1 TYR 484 33.244 −33.735 84.668 1.00 44.09 ATOM 2284 CE1 TYR 484 33.210 −34.148 86.000 1.00 43.91 ATOM 2285 CD2 TYR 484 32.113 −31.714 85.255 1.00 43.24 ATOM 2286 CE2 TYR 484 32.074 −32.121 86.588 1.00 42.95 ATOM 2287 CZ TYR 484 32.624 −33.337 86.950 1.00 42.55 ATOM 2288 OH TYR 484 32.605 −33.739 88.263 1.00 43.56 ATOM 2289 C TYR 484 31.316 −34.120 82.176 1.00 43.44 ATOM 2290 O TYR 484 31.810 −34.877 81.327 1.00 42.64 ATOM 2291 N LYS 485 30.622 −34.562 83.221 1.00 43.25 ATOM 2292 CA LYS 485 30.424 −35.989 83.449 1.00 44.97 ATOM 2293 CB LYS 485 30.249 −36.265 84.946 1.00 46.94 ATOM 2294 CG LYS 485 29.083 −35.540 85.606 1.00 49.26 ATOM 2295 CD LYS 485 29.109 −35.779 87.115 1.00 53.35 ATOM 2296 CE LYS 485 28.091 −34.913 87.862 1.00 55.98 ATOM 2297 NZ LYS 485 28.190 −35.067 89.350 1.00 55.85 ATOM 2298 C LYS 485 29.230 −36.557 82.686 1.00 44.79 ATOM 2299 O LYS 485 28.637 −37.547 83.105 1.00 45.03 ATOM 2300 N TYR 486 28.876 −35.931 81.568 1.00 43.62 ATOM 2301 CA TYR 486 27.750 −36.389 80.767 1.00 41.82 ATOM 2302 CB TYR 486 26.523 −35.492 80.970 1.00 38.82 ATOM 2303 CG TYR 486 25.915 −35.521 82.350 1.00 36.43 ATOM 2304 CD1 TYR 486 26.240 −34.550 83.299 1.00 37.04 ATOM 2305 CE1 TYR 486 25.677 −34.577 84.576 1.00 36.71 ATOM 2306 CD2 TYR 486 25.011 −36.514 82.709 1.00 34.16 ATOM 2307 CE2 TYR 486 24.445 −36.550 83.979 1.00 33.33 ATOM 2308 CZ TYR 486 24.777 −35.583 84.904 1.00 34.49 ATOM 2309 OH TYR 486 24.220 −35.624 86.158 1.00 34.00 ATOM 2310 C TYR 486 28.089 −36.382 79.291 1.00 42.66 ATOM 2311 O TYR 486 29.078 −35.796 78.866 1.00 44.53 ATOM 2312 N LYS 487 27.249 −37.041 78.509 1.00 43.23 ATOM 2313 CA LYS 487 27.413 −37.090 77.070 1.00 43.39 ATOM 2314 CB LYS 487 28.638 −37.915 76.670 1.00 42.59 ATOM 2315 CG LYS 487 28.399 −39.401 76.615 1.00 42.82 ATOM 2316 CD LYS 487 29.518 −40.088 75.855 1.00 45.58 ATOM 2317 CE LYS 487 29.612 −39.594 74.405 1.00 46.48 ATOM 2318 NZ LYS 487 30.745 −40.213 73.638 1.00 44.44 ATOM 2319 C LYS 487 26.149 −37.724 76.527 1.00 43.48 ATOM 2320 O LYS 487 25.597 −38.640 77.128 1.00 43.29 ATOM 2321 N VAL 488 25.682 −37.217 75.400 1.00 44.12 ATOM 2322 CA VAL 488 24.475 −37.729 74.790 1.00 45.91 ATOM 2323 CB VAL 488 23.558 −36.554 74.409 1.00 44.11 ATOM 2324 CG1 VAL 488 24.209 −35.720 73.338 1.00 44.27 ATOM 2325 CG2 VAL 488 22.214 −37.056 73.966 1.00 44.39 ATOM 2326 C VAL 488 24.864 −38.554 73.557 1.00 48.36 ATOM 2327 O VAL 488 25.888 −38.290 72.927 1.00 48.88 ATOM 2328 N VAL 489 24.070 −39.570 73.223 1.00 51.09 ATOM 2329 CA VAL 489 24.383 −40.403 72.060 1.00 53.62 ATOM 2330 CB VAL 489 25.341 −41.573 72.438 1.00 53.16 ATOM 2331 CG1 VAL 489 24.659 −42.513 73.409 1.00 51.07 ATOM 2332 CG2 VAL 489 25.783 −42.316 71.178 1.00 52.29 ATOM 2333 C VAL 489 23.161 −40.983 71.344 1.00 55.28 ATOM 2334 O VAL 489 22.115 −41.249 71.956 1.00 55.15 ATOM 2335 N LYS 490 23.317 −41.163 70.033 1.00 56.80 ATOM 2336 CA LYS 490 22.272 −41.708 69.179 1.00 58.05 ATOM 2337 CB LYS 490 22.757 −41.833 67.729 1.00 59.78 ATOM 2338 CG LYS 490 23.172 −40.539 67.031 1.00 63.37 ATOM 2339 CD LYS 490 24.493 −39.974 67.570 1.00 66.32 ATOM 2340 CE LYS 490 25.132 −38.975 66.597 1.00 66.85 ATOM 2341 NZ LYS 490 24.183 −37.926 66.111 1.00 68.56 ATOM 2342 C LYS 490 21.928 −43.094 69.671 1.00 57.96 ATOM 2343 O LYS 490 22.825 −43.917 69.873 1.00 58.39 ATOM 2344 N ILE 491 20.642 −43.364 69.868 1.00 57.59 ATOM 2345 CA ILE 491 20.237 −44.697 70.303 1.00 56.42 ATOM 2346 CB ILE 491 18.861 −44.685 70.982 1.00 53.57 ATOM 2347 CG2 ILE 491 18.641 −45.994 71.698 1.00 52.55 ATOM 2348 CG1 ILE 491 18.776 −43.545 71.983 1.00 52.06 ATOM 2349 CD1 ILE 491 17.409 −43.403 72.594 1.00 50.94 ATOM 2350 C ILE 491 20.144 −45.570 69.045 1.00 57.42 ATOM 2351 O ILE 491 19.728 −45.038 67.989 1.00 57.28 ATOM 2352 OXT ILE 491 20.478 −46.769 69.127 1.00 58.91 END VII. Crystals of gp120 with an Extended V3 Loop

The present disclosure further relates to the crystal structure of gp120 in which the V3 loop is in an extended conformation. The present disclosure also relates to the crystals obtained from a gp120 polypeptide with an extended V3 loop. The three-dimensional coordinates of a gp120 polypeptide with an extended V3 loop, three-dimensional structures of models of a gp120 polypeptide with an extended V3 loop, and uses of these models. The amino acid sequence of a gp120 polypeptide with an extended V3 loop variant is set forth as SEQ ID NO: 2.

The structure of a gp120 polypeptide with an extended V3 loop was solved in complex with the X5 Fab and the d1d2 domain of the CD4 receptor. Analysis of the structure revealed that the V3 loop was present in an elongated conformation that was previously not seen in other complexes involving the gp120 protein. An advantageous feature of this crystal structure over previous structures is the organization of the V3 loop in an elongated conformation, compatible with the elicitation of immunodominant antibody response. Table 2 provides the atomic coordinates of the crystal structure of the polypeptide disclosed in SEQ ID NO: 2.

TABLE 2 The structural coordinates of an exemplary gp120 with an extended V3 loop ATOM 1 N VAL G 84 83.090 −158.764 98.727 1.00 133.29 ATOM 2 CA VAL G 84 84.569 −158.842 98.897 1.00 133.95 ATOM 3 C VAL G 84 85.258 −158.165 97.714 1.00 134.16 ATOM 4 O VAL G 84 85.855 −158.828 96.866 1.00 134.41 ATOM 5 CB VAL G 84 85.039 −160.312 98.978 1.00 134.07 ATOM 6 CG1 VAL G 84 86.507 −160.372 99.373 1.00 134.72 ATOM 7 CG2 VAL G 84 84.181 −161.078 99.974 1.00 132.76 ATOM 8 N VAL G 85 85.169 −156.839 97.667 1.00 134.17 ATOM 9 CA VAL G 85 85.767 −156.061 96.587 1.00 133.97 ATOM 10 C VAL G 85 87.243 −155.768 96.832 1.00 134.16 ATOM 11 O VAL G 85 87.711 −155.788 97.971 1.00 134.47 ATOM 12 CB VAL G 85 85.026 −154.715 96.401 1.00 133.69 ATOM 13 CG1 VAL G 85 85.141 −153.883 97.666 1.00 133.08 ATOM 14 CG2 VAL G 85 85.601 −153.958 95.213 1.00 133.51 ATOM 15 N LEU G 86 87.971 −155.505 95.751 1.00 134.10 ATOM 16 CA LEU G 86 89.392 −155.192 95.827 1.00 134.30 ATOM 17 C LEU G 86 89.724 −154.045 94.874 1.00 134.27 ATOM 18 O LEU G 86 90.077 −154.264 93.714 1.00 134.21 ATOM 19 CB LEU G 86 90.235 −156.426 95.483 1.00 134.49 ATOM 20 CG LEU G 86 90.134 −157.616 96.446 1.00 134.44 ATOM 21 CD1 LEU G 86 88.803 −158.331 96.264 1.00 134.35 ATOM 22 CD2 LEU G 86 91.277 −158.581 96.183 1.00 134.28 ATOM 23 N GLU G 87 89.663 −152.780 95.269 1.00 136.00 ATOM 24 CA GLU G 87 89.975 −151.658 94.374 1.00 136.69 ATOM 25 C GLU G 87 91.472 −151.398 94.342 1.00 137.59 ATOM 26 O GLU G 87 92.122 −151.341 95.383 1.00 138.06 ATOM 27 CB GLU G 87 89.285 −150.383 94.827 1.00 135.94 ATOM 28 CG GLU G 87 87.799 −150.526 94.988 1.00 136.55 ATOM 29 CD GLU G 87 87.274 −149.713 96.220 1.00 137.15 ATOM 30 OE1 GLU G 87 88.011 −149.739 97.285 1.00 138.80 ATOM 31 OE2 GLU G 87 86.143 −149.072 96.141 1.00 137.57 ATOM 32 N ASN G 88 91.857 −151.247 93.247 1.00 136.70 ATOM 33 CA ASN G 88 93.272 −150.981 92.995 1.00 137.44 ATOM 34 C ASN G 88 93.532 −149.487 92.827 1.00 138.14 ATOM 35 O ASN G 88 93.615 −148.984 91.707 1.00 138.46 ATOM 36 CB ASN G 88 93.735 −151.732 91.741 1.00 137.16 ATOM 37 CG ASN G 88 95.046 −151.199 91.192 1.00 137.46 ATOM 38 OD1 ASN G 88 96.022 −151.042 91.924 1.00 137.34 ATOM 39 ND2 ASN G 88 95.074 −150.921 89.892 1.00 138.00 ATOM 40 N VAL G 89 93.664 −148.778 93.944 1.00 138.65 ATOM 41 CA VAL G 89 93.906 −147.342 93.893 1.00 138.82 ATOM 42 C VAL G 89 94.756 −146.842 95.059 1.00 139.51 ATOM 43 O VAL G 89 94.835 −147.483 96.108 1.00 139.82 ATOM 44 CB VAL G 89 92.570 −146.564 93.877 1.00 138.22 ATOM 45 CG1 VAL G 89 91.797 −146.834 95.158 1.00 137.56 ATOM 46 CG2 VAL G 89 92.830 −145.076 93.703 1.00 137.89 ATOM 47 N THR G 90 95.394 −145.693 94.856 1.00 139.18 ATOM 48 CA THR G 90 96.233 −145.076 95.874 1.00 138.77 ATOM 49 C THR G 90 95.355 −144.357 96.903 1.00 137.61 ATOM 50 O THR G 90 94.887 −143.241 96.671 1.00 137.17 ATOM 51 CB THR G 90 97.224 −144.075 95.229 1.00 139.07 ATOM 52 OG1 THR G 90 97.906 −143.340 96.252 1.00 139.89 ATOM 53 CG2 THR G 90 96.490 −143.113 94.303 1.00 138.94 ATOM 54 N GLU G 91 95.133 −145.015 98.038 1.00 136.88 ATOM 55 CA GLU G 91 94.302 −144.480 99.117 1.00 136.34 ATOM 56 C GLU G 91 94.989 −143.439 99.999 1.00 136.12 ATOM 57 O GLU G 91 95.991 −143.730 100.653 1.00 136.07 ATOM 58 CB GLU G 91 93.806 −145.627 100.002 1.00 135.71 ATOM 59 CG GLU G 91 92.609 −146.385 99.457 1.00 134.03 ATOM 60 CD GLU G 91 91.293 −145.844 99.980 1.00 132.56 ATOM 61 OE1 GLU G 91 90.982 −144.661 99.725 1.00 131.44 ATOM 62 OE2 GLU G 91 90.568 −146.606 100.653 1.00 131.61 ATOM 63 N HIS G 92 94.430 −142.231 100.027 1.00 135.50 ATOM 64 CA HIS G 92 94.973 −141.145 100.838 1.00 134.96 ATOM 65 C HIS G 92 94.490 −141.268 102.282 1.00 133.04 ATOM 66 O HIS G 92 93.411 −141.798 102.537 1.00 133.15 ATOM 67 CB HIS G 92 94.541 −139.793 100.266 1.00 138.44 ATOM 68 CG HIS G 92 95.064 −139.522 98.889 1.00 142.66 ATOM 69 ND1 HIS G 92 94.870 −138.319 98.245 1.00 144.46 ATOM 70 CD2 HIS G 92 95.775 −140.296 98.035 1.00 143.67 ATOM 71 CE1 HIS G 92 95.441 −138.362 97.054 1.00 145.80 ATOM 72 NE2 HIS G 92 95.997 −139.551 96.902 1.00 145.38 ATOM 73 N PHE G 93 95.289 −140.768 103.221 1.00 130.39 ATOM 74 CA PHE G 93 94.950 −140.836 104.640 1.00 126.69 ATOM 75 C PHE G 93 95.478 −139.628 105.413 1.00 125.30 ATOM 76 O PHE G 93 96.479 −139.026 105.033 1.00 125.23 ATOM 77 CB PHE G 93 95.534 −142.115 105.247 1.00 125.14 ATOM 78 CG PHE G 93 94.502 −143.095 105.721 1.00 123.03 ATOM 79 CD1 PHE G 93 93.494 −143.538 104.871 1.00 122.34 ATOM 80 CD2 PHE G 93 94.558 −143.600 107.013 1.00 122.41 ATOM 81 CE1 PHE G 93 92.556 −144.470 105.304 1.00 121.87 ATOM 82 CE2 PHE G 93 93.626 −144.532 107.456 1.00 121.75 ATOM 83 CZ PHE G 93 92.623 −144.969 106.599 1.00 121.40 ATOM 84 N ASN G 94 94.800 −139.283 106.502 1.00 123.37 ATOM 85 CA ASN G 94 95.207 −138.158 107.336 1.00 121.13 ATOM 86 C ASN G 94 94.643 −138.370 108.735 1.00 120.97 ATOM 87 O ASN G 94 93.696 −139.136 108.918 1.00 121.62 ATOM 88 CB ASN G 94 94.677 −136.839 106.762 1.00 118.89 ATOM 89 CG ASN G 94 95.603 −135.670 107.034 1.00 116.56 ATOM 90 OD1 ASN G 94 96.617 −135.501 106.358 1.00 115.47 ATOM 91 ND2 ASN G 94 95.266 −134.863 108.033 1.00 115.47 ATOM 92 N MET G 95 95.217 −137.687 109.719 1.00 120.03 ATOM 93 CA MET G 95 94.754 −137.820 111.094 1.00 119.35 ATOM 94 C MET G 95 94.581 −136.459 111.751 1.00 118.97 ATOM 95 O MET G 95 93.918 −136.332 112.780 1.00 118.34 ATOM 96 CB MET G 95 95.750 −138.658 111.900 1.00 119.23 ATOM 97 CG MET G 95 97.163 −138.093 111.906 1.00 119.40 ATOM 98 SD MET G 95 98.323 −139.128 112.817 1.00 118.08 ATOM 99 CE MET G 95 98.176 −138.435 114.461 1.00 119.02 ATOM 100 N TRP G 96 95.175 −135.438 111.144 1.00 119.91 ATOM 101 CA TRP G 96 95.102 −134.087 111.683 1.00 121.52 ATOM 102 C TRP G 96 93.868 −133.346 111.184 1.00 123.34 ATOM 103 O TRP G 96 93.242 −132.601 111.935 1.00 123.67 ATOM 104 CB TRP G 96 96.371 −133.312 111.323 1.00 120.30 ATOM 105 CG TRP G 96 97.616 −134.122 111.530 1.00 119.93 ATOM 106 CD1 TRP G 96 98.257 −134.889 110.599 1.00 119.95 ATOM 107 CD2 TRP G 96 98.326 −134.309 112.761 1.00 119.57 ATOM 108 NE1 TRP G 96 99.321 −135.544 111.174 1.00 119.53 ATOM 109 CE2 TRP G 96 99.387 −135.204 112.498 1.00 119.10 ATOM 110 CE3 TRP G 96 98.170 −133.805 114.058 1.00 119.39 ATOM 111 CZ2 TRP G 96 100.285 −135.611 113.490 1.00 118.59 ATOM 112 CZ3 TRP G 96 99.064 −134.210 115.043 1.00 117.94 ATOM 113 CH2 TRP G 96 100.109 −135.103 114.751 1.00 117.96 ATOM 114 N LYS G 97 93.519 −133.549 109.919 1.00 125.13 ATOM 115 CA LYS G 97 92.338 −132.906 109.350 1.00 127.15 ATOM 116 C LYS G 97 91.243 −133.960 109.235 1.00 127.03 ATOM 117 O LYS G 97 90.591 −134.084 108.201 1.00 127.49 ATOM 118 CB LYS G 97 92.656 −132.324 107.965 1.00 128.56 ATOM 119 CG LYS G 97 92.419 −130.817 107.836 1.00 130.40 ATOM 120 CD LYS G 97 93.554 −129.998 108.449 1.00 131.70 ATOM 121 CE LYS G 97 94.673 −129.727 107.447 1.00 132.45 ATOM 122 NZ LYS G 97 94.251 −128.765 106.387 1.00 132.15 ATOM 123 N ASN G 98 91.056 −134.719 110.309 1.00 127.04 ATOM 124 CA ASN G 98 90.060 −135.781 110.347 1.00 127.06 ATOM 125 C ASN G 98 88.846 −135.370 111.174 1.00 126.76 ATOM 126 O ASN G 98 88.979 −134.956 112.325 1.00 127.98 ATOM 127 CB ASN G 98 90.692 −137.051 110.924 1.00 126.57 ATOM 128 CG ASN G 98 89.763 −138.242 110.877 1.00 125.98 ATOM 129 OD1 ASN G 98 88.791 −138.254 110.124 1.00 126.75 ATOM 130 ND2 ASN G 98 90.067 −139.262 111.670 1.00 125.44 ATOM 131 N ASP G 99 87.665 −135.494 110.580 1.00 125.41 ATOM 132 CA ASP G 99 86.426 −135.125 111.251 1.00 124.29 ATOM 133 C ASP G 99 86.042 −136.161 112.303 1.00 122.94 ATOM 134 O ASP G 99 85.313 −135.865 113.253 1.00 123.21 ATOM 135 CB ASP G 99 85.309 −134.984 110.213 1.00 125.07 ATOM 136 CG ASP G 99 84.039 −134.383 110.792 1.00 125.46 ATOM 137 OD1 ASP G 99 83.255 −135.132 111.407 1.00 125.32 ATOM 138 OD2 ASP G 99 83.839 −133.158 110.637 1.00 125.35 ATOM 139 N MET G 100 86.548 −137.376 112.128 1.00 121.29 ATOM 140 CA MET G 100 86.264 −138.472 113.044 1.00 120.02 ATOM 141 C MET G 100 86.815 −138.176 114.432 1.00 119.25 ATOM 142 O MET G 100 86.282 −138.649 115.436 1.00 118.87 ATOM 143 CB MET G 100 86.879 −139.768 112.510 1.00 119.67 ATOM 144 CG MET G 100 86.385 −141.023 113.205 1.00 120.23 ATOM 145 SD MET G 100 87.433 −142.456 112.875 1.00 121.05 ATOM 146 CE MET G 100 86.737 −143.078 111.340 1.00 122.33 ATOM 147 N VAL G 101 87.887 −137.395 114.482 1.00 118.47 ATOM 148 CA VAL G 101 88.514 −137.038 115.748 1.00 117.12 ATOM 149 C VAL G 101 87.713 −135.967 116.472 1.00 115.61 ATOM 150 O VAL G 101 87.466 −136.072 117.671 1.00 114.97 ATOM 151 CB VAL G 101 89.943 −136.515 115.529 1.00 117.83 ATOM 152 CG1 VAL G 101 90.577 −136.163 116.863 1.00 119.14 ATOM 153 CG2 VAL G 101 90.770 −137.564 114.807 1.00 118.81 ATOM 154 N GLU G 102 87.305 −134.938 115.738 1.00 115.04 ATOM 155 CA GLU G 102 86.523 −133.862 116.330 1.00 115.24 ATOM 156 C GLU G 102 85.146 −134.344 116.762 1.00 114.28 ATOM 157 O GLU G 102 84.557 −133.812 117.702 1.00 113.48 ATOM 158 CB GLU G 102 86.367 −132.695 115.347 1.00 116.69 ATOM 159 CG GLU G 102 87.576 −131.763 115.267 1.00 118.95 ATOM 160 CD GLU G 102 88.647 −132.239 114.301 1.00 120.98 ATOM 161 OE1 GLU G 102 88.576 −131.886 113.102 1.00 121.42 ATOM 162 OE2 GLU G 102 89.561 −132.969 114.738 1.00 121.86 ATOM 163 N GLN G 103 84.634 −135.357 116.076 1.00 114.05 ATOM 164 CA GLN G 103 83.319 −135.893 116.395 1.00 114.16 ATOM 165 C GLN G 103 83.404 −136.708 117.681 1.00 113.15 ATOM 166 O GLN G 103 82.510 −136.657 118.525 1.00 113.27 ATOM 167 CB GLN G 103 82.824 −136.756 115.230 1.00 116.01 ATOM 168 CG GLN G 103 81.313 −136.831 115.089 1.00 118.46 ATOM 169 CD GLN G 103 80.887 −137.109 113.660 1.00 120.20 ATOM 170 OE1 GLN G 103 81.169 −138.173 113.109 1.00 121.62 ATOM 171 NE2 GLN G 103 80.208 −136.143 113.048 1.00 120.70 ATOM 172 N MET G 104 84.497 −137.450 117.823 1.00 112.25 ATOM 173 CA MET G 104 84.730 −138.274 119.004 1.00 111.54 ATOM 174 C MET G 104 84.838 −137.376 120.232 1.00 112.25 ATOM 175 O MET G 104 84.313 −137.689 121.299 1.00 112.78 ATOM 176 CB MET G 104 86.028 −139.071 118.840 1.00 110.90 ATOM 177 CG MET G 104 86.435 −139.867 120.071 1.00 109.19 ATOM 178 SD MET G 104 85.518 −141.402 120.304 1.00 108.60 ATOM 179 CE MET G 104 86.816 −142.479 120.947 1.00 106.86 ATOM 180 N GLN G 105 85.530 −136.256 120.063 1.00 112.10 ATOM 181 CA GLN G 105 85.726 −135.286 121.134 1.00 111.89 ATOM 182 C GLN G 105 84.399 −134.844 121.744 1.00 112.91 ATOM 183 O GLN G 105 84.246 −134.807 122.963 1.00 113.09 ATOM 184 CB GLN G 105 86.475 −134.064 120.588 1.00 110.93 ATOM 185 CG GLN G 105 86.461 −132.848 121.498 1.00 108.92 ATOM 186 CD GLN G 105 87.579 −132.849 122.518 1.00 108.26 ATOM 187 OE1 GLN G 105 87.613 −132.002 123.408 1.00 108.65 ATOM 188 NE2 GLN G 105 88.505 −133.792 122.388 1.00 108.60 ATOM 189 N GLU G 106 83.443 −134.516 120.882 1.00 113.95 ATOM 190 CA GLU G 106 82.123 −134.062 121.310 1.00 114.14 ATOM 191 C GLU G 106 81.423 −135.064 122.216 1.00 112.47 ATOM 192 O GLU G 106 80.694 −134.683 123.129 1.00 111.33 ATOM 193 CB GLU G 106 81.240 −133.790 120.085 1.00 117.22 ATOM 194 CG GLU G 106 81.847 −132.829 119.069 1.00 121.88 ATOM 195 CD GLU G 106 81.831 −131.385 119.534 1.00 124.83 ATOM 196 OE1 GLU G 106 80.725 −130.827 119.702 1.00 127.31 ATOM 197 OE2 GLU G 106 82.922 −130.809 119.731 1.00 125.75 ATOM 198 N ASP G 107 81.651 −136.347 121.961 1.00 112.07 ATOM 199 CA ASP G 107 81.025 −137.407 122.739 1.00 112.28 ATOM 200 C ASP G 107 81.683 −137.674 124.079 1.00 110.45 ATOM 201 O ASP G 107 81.034 −138.143 125.012 1.00 110.76 ATOM 202 CB ASP G 107 80.989 −138.693 121.918 1.00 114.84 ATOM 203 CG ASP G 107 79.945 −138.646 120.814 1.00 117.49 ATOM 204 OD1 ASP G 107 78.775 −138.970 121.099 1.00 120.99 ATOM 205 OD2 ASP G 107 80.294 −138.268 119.674 1.00 117.70 ATOM 206 N ILE G 108 82.972 −137.386 124.181 1.00 108.33 ATOM 207 CA ILE G 108 83.680 −137.603 125.432 1.00 106.57 ATOM 208 C ILE G 108 83.295 −136.515 126.419 1.00 104.72 ATOM 209 O ILE G 108 83.130 −136.771 127.611 1.00 105.07 ATOM 210 CB ILE G 108 85.194 −137.592 125.199 1.00 107.34 ATOM 211 CG1 ILE G 108 85.570 −138.780 124.303 1.00 106.62 ATOM 212 CG2 ILE G 108 85.931 −137.666 126.532 1.00 107.53 ATOM 213 CD1 ILE G 108 86.711 −138.511 123.364 1.00 106.38 ATOM 214 N ILE G 109 83.140 −135.301 125.909 1.00 102.38 ATOM 215 CA ILE G 109 82.755 −134.174 126.740 1.00 100.25 ATOM 216 C ILE G 109 81.357 −134.416 127.284 1.00 99.75 ATOM 217 O ILE G 109 81.073 −134.128 128.443 1.00 100.09 ATOM 218 CB ILE G 109 82.758 −132.871 125.925 1.00 99.79 ATOM 219 CG1 ILE G 109 84.181 −132.570 125.447 1.00 98.40 ATOM 220 CG2 ILE G 109 82.219 −131.728 126.764 1.00 99.76 ATOM 221 CD1 ILE G 109 84.271 −131.441 124.449 1.00 97.98 ATOM 222 N SER G 110 80.493 −134.963 126.436 1.00 99.49 ATOM 223 CA SER G 110 79.120 −135.258 126.819 1.00 99.12 ATOM 224 C SER G 110 79.098 −136.336 127.897 1.00 99.07 ATOM 225 O SER G 110 78.261 −136.317 128.797 1.00 98.54 ATOM 226 CB SER G 110 78.329 −135.732 125.601 1.00 99.18 ATOM 227 OG SER G 110 76.996 −136.053 125.961 1.00 99.12 ATOM 228 N LEU G 111 80.029 −137.276 127.793 1.00 99.33 ATOM 229 CA LEU G 111 80.135 −138.364 128.755 1.00 100.48 ATOM 230 C LEU G 111 80.790 −137.873 130.041 1.00 101.49 ATOM 231 O LEU G 111 80.609 −138.458 131.109 1.00 101.29 ATOM 232 CB LEU G 111 80.952 −139.511 128.155 1.00 100.12 ATOM 233 CG LEU G 111 80.176 −140.676 127.531 1.00 100.14 ATOM 234 CD1 LEU G 111 80.992 −141.321 126.426 1.00 100.57 ATOM 235 CD2 LEU G 111 79.843 −141.684 128.621 1.00 100.82 ATOM 236 N TRP G 112 81.553 −136.791 129.928 1.00 103.03 ATOM 237 CA TRP G 112 82.238 −136.210 131.076 1.00 104.23 ATOM 238 C TRP G 112 81.265 −135.378 131.896 1.00 105.45 ATOM 239 O TRP G 112 81.329 −135.357 133.122 1.00 106.05 ATOM 240 CB TRP G 112 83.402 −135.326 130.612 1.00 103.46 ATOM 241 CG TRP G 112 84.730 −135.748 131.159 1.00 102.75 ATOM 242 CD1 TRP G 112 85.403 −136.903 130.881 1.00 103.42 ATOM 243 CD2 TRP G 112 85.550 −135.017 132.080 1.00 101.80 ATOM 244 NE1 TRP G 112 86.593 −136.936 131.570 1.00 103.39 ATOM 245 CE2 TRP G 112 86.708 −135.792 132.313 1.00 101.79 ATOM 246 CE3 TRP G 112 85.418 −133.783 132.730 1.00 100.62 ATOM 247 CZ2 TRP G 112 87.730 −135.371 133.171 1.00 100.65 ATOM 248 CZ3 TRP G 112 86.435 −133.366 133.582 1.00 100.30 ATOM 249 CH2 TRP G 112 87.576 −134.160 133.793 1.00 100.15 ATOM 250 N ASP G 113 80.361 −134.693 131.207 1.00 106.82 ATOM 251 CA ASP G 113 79.376 −133.862 131.879 1.00 108.44 ATOM 252 C ASP G 113 78.342 −134.672 132.643 1.00 108.41 ATOM 253 O ASP G 113 77.709 −134.157 133.563 1.00 108.64 ATOM 254 CB ASP G 113 78.673 −132.951 130.875 1.00 110.86 ATOM 255 CG ASP G 113 79.477 −131.700 130.566 1.00 113.42 ATOM 256 OD1 ASP G 113 79.640 −130.866 131.479 1.00 116.27 ATOM 257 OD2 ASP G 113 79.955 −131.560 129.420 1.00 115.26 ATOM 258 N GLN G 114 78.160 −135.936 132.273 1.00 107.17 ATOM 259 CA GLN G 114 77.188 −136.766 132.974 1.00 106.10 ATOM 260 C GLN G 114 77.874 −137.744 133.923 1.00 103.76 ATOM 261 O GLN G 114 77.242 −138.651 134.461 1.00 104.43 ATOM 262 CB GLN G 114 76.300 −137.527 131.980 1.00 109.06 ATOM 263 CG GLN G 114 77.005 −138.596 131.161 1.00 113.60 ATOM 264 CD GLN G 114 76.029 −139.502 130.422 1.00 116.46 ATOM 265 OE1 GLN G 114 75.346 −139.076 129.488 1.00 118.64 ATOM 266 NE2 GLN G 114 75.951 −140.758 130.850 1.00 116.28 ATOM 267 N SER G 115 79.172 −137.543 134.127 1.00 100.33 ATOM 268 CA SER G 115 79.956 −138.393 135.014 1.00 96.91 ATOM 269 C SER G 115 80.706 −137.560 136.051 1.00 93.15 ATOM 270 O SER G 115 80.543 −137.758 137.255 1.00 93.21 ATOM 271 CB SER G 115 80.946 −139.233 134.203 1.00 99.27 ATOM 272 OG SER G 115 80.275 −140.234 133.457 1.00 102.68 ATOM 273 N LEU G 116 81.527 −136.629 135.581 1.00 88.46 ATOM 274 CA LEU G 116 82.290 −135.766 136.475 1.00 84.39 ATOM 275 C LEU G 116 81.741 −134.347 136.459 1.00 82.46 ATOM 276 O LEU G 116 81.977 −133.591 135.519 1.00 82.86 ATOM 277 CB LEU G 116 83.767 −135.750 136.068 1.00 83.85 ATOM 278 CG LEU G 116 84.646 −136.857 136.656 1.00 82.12 ATOM 279 CD1 LEU G 116 85.974 −136.902 135.922 1.00 82.50 ATOM 280 CD2 LEU G 116 84.854 −136.596 138.144 1.00 80.96 ATOM 281 N LYS G 117 81.000 −133.995 137.503 1.00 80.71 ATOM 282 CA LYS G 117 80.407 −132.668 137.619 1.00 80.17 ATOM 283 C LYS G 117 81.100 −131.822 138.683 1.00 77.80 ATOM 284 O LYS G 117 81.342 −132.288 139.797 1.00 77.93 ATOM 285 CB LYS G 117 78.921 −132.780 137.955 1.00 82.16 ATOM 286 CG LYS G 117 77.997 −133.018 136.772 1.00 85.17 ATOM 287 CD LYS G 117 76.551 −132.954 137.242 1.00 87.66 ATOM 288 CE LYS G 117 75.607 −132.504 136.137 1.00 90.61 ATOM 289 NZ LYS G 117 74.283 −132.090 136.692 1.00 87.92 ATOM 290 N PRO G 118 81.420 −130.558 138.355 1.00 75.68 ATOM 291 CA PRO G 118 82.088 −129.645 139.284 1.00 74.22 ATOM 292 C PRO G 118 81.059 −129.021 140.206 1.00 73.71 ATOM 293 O PRO G 118 79.881 −128.947 139.863 1.00 75.64 ATOM 294 CB PRO G 118 82.709 −128.596 138.358 1.00 73.60 ATOM 295 CG PRO G 118 82.659 −129.228 136.975 1.00 74.73 ATOM 296 CD PRO G 118 81.352 −129.945 137.022 1.00 75.01 ATOM 297 N CYS G 119 81.481 −128.570 141.377 1.00 73.04 ATOM 298 CA CYS G 119 80.517 −127.953 142.264 1.00 73.80 ATOM 299 C CYS G 119 80.324 −126.491 141.888 1.00 72.46 ATOM 300 O CYS G 119 79.284 −125.907 142.171 1.00 73.82 ATOM 301 CB CYS G 119 80.944 −128.105 143.722 1.00 77.08 ATOM 302 SG CYS G 119 79.924 −129.360 144.564 1.00 86.22 ATOM 303 N VAL G 120 81.326 −125.907 141.241 1.00 69.39 ATOM 304 CA VAL G 120 81.247 −124.524 140.795 1.00 66.24 ATOM 305 C VAL G 120 81.939 −124.437 139.445 1.00 66.78 ATOM 306 O VAL G 120 83.008 −125.008 139.260 1.00 67.35 ATOM 307 CB VAL G 120 81.964 −123.562 141.757 1.00 65.45 ATOM 308 CG1 VAL G 120 81.757 −122.128 141.292 1.00 64.25 ATOM 309 CG2 VAL G 120 81.448 −123.745 143.167 1.00 65.16 ATOM 310 N LYS G 121 81.321 −123.744 138.498 1.00 68.69 ATOM 311 CA LYS G 121 81.903 −123.590 137.170 1.00 71.74 ATOM 312 C LYS G 121 82.060 −122.128 136.796 1.00 74.27 ATOM 313 O LYS G 121 81.131 −121.337 136.959 1.00 76.19 ATOM 314 CB LYS G 121 81.033 −124.260 136.099 1.00 72.94 ATOM 315 CG LYS G 121 81.448 −125.664 135.700 1.00 75.20 ATOM 316 CD LYS G 121 80.779 −126.073 134.387 1.00 77.11 ATOM 317 CE LYS G 121 81.061 −127.533 134.049 1.00 78.09 ATOM 318 NZ LYS G 121 80.615 −127.906 132.674 1.00 79.45 ATOM 319 N LEU G 122 83.233 −121.767 136.290 1.00 76.38 ATOM 320 CA LEU G 122 83.473 −120.394 135.863 1.00 79.17 ATOM 321 C LEU G 122 83.757 −120.376 134.371 1.00 81.74 ATOM 322 O LEU G 122 84.701 −121.010 133.905 1.00 82.55 ATOM 323 CB LEU G 122 84.657 −119.785 136.611 1.00 79.45 ATOM 324 CG LEU G 122 84.274 −118.875 137.779 1.00 78.85 ATOM 325 CD1 LEU G 122 83.608 −119.695 138.873 1.00 77.90 ATOM 326 CD2 LEU G 122 85.521 −118.189 138.306 1.00 79.94 ATOM 327 N THR G 123 82.938 −119.641 133.629 1.00 85.43 ATOM 328 CA THR G 123 83.092 −119.563 132.186 1.00 90.13 ATOM 329 C THR G 123 83.058 −118.134 131.670 1.00 93.59 ATOM 330 O THR G 123 82.259 −117.321 132.126 1.00 94.38 ATOM 331 CB THR G 123 81.968 −120.333 131.489 1.00 91.32 ATOM 332 OG1 THR G 123 81.834 −121.630 132.076 1.00 93.24 ATOM 333 CG2 THR G 123 82.256 −120.494 130.011 1.00 91.25 ATOM 334 N PRO G 124 83.927 −117.810 130.700 1.00 97.34 ATOM 335 CA PRO G 124 83.953 −116.456 130.148 1.00 100.80 ATOM 336 C PRO G 124 82.656 −116.141 129.415 1.00 103.51 ATOM 337 O PRO G 124 82.392 −116.686 128.346 1.00 104.31 ATOM 338 CB PRO G 124 85.163 −116.493 129.211 1.00 100.91 ATOM 339 CG PRO G 124 86.068 −117.489 129.882 1.00 100.12 ATOM 340 CD PRO G 124 85.075 −118.584 130.199 1.00 98.73 ATOM 341 N LEU G 125 81.838 −115.271 129.994 1.00 107.90 ATOM 342 CA LEU G 125 80.575 −114.898 129.366 1.00 112.76 ATOM 343 C LEU G 125 80.861 −113.904 128.250 1.00 116.09 ATOM 344 O LEU G 125 80.624 −112.709 128.406 1.00 116.30 ATOM 345 CB LEU G 125 79.648 −114.256 130.398 1.00 113.40 ATOM 346 CG LEU G 125 78.192 −114.016 129.992 1.00 113.32 ATOM 347 CD1 LEU G 125 77.403 −115.309 130.161 1.00 114.30 ATOM 348 CD2 LEU G 125 77.599 −112.929 130.874 1.00 114.10 ATOM 349 N CYS G 126 81.378 −114.395 127.128 1.00 119.58 ATOM 350 CA CYS G 126 81.708 −113.515 126.016 1.00 122.95 ATOM 351 C CYS G 126 80.573 −113.191 125.057 1.00 125.81 ATOM 352 O CYS G 126 80.494 −113.734 123.953 1.00 126.35 ATOM 353 CB CYS G 126 82.901 −114.067 125.236 1.00 122.36 ATOM 354 SG CYS G 126 84.494 −113.726 126.046 1.00 121.90 ATOM 355 N VAL G 127 79.696 −112.296 125.497 1.00 129.15 ATOM 356 CA VAL G 127 78.566 −111.852 124.693 1.00 131.76 ATOM 357 C VAL G 127 78.834 −110.393 124.326 1.00 132.26 ATOM 358 O VAL G 127 79.182 −109.582 125.187 1.00 132.30 ATOM 359 CB VAL G 127 77.241 −111.952 125.483 1.00 132.38 ATOM 360 CG1 VAL G 127 77.304 −111.072 126.721 1.00 133.33 ATOM 361 CG2 VAL G 127 76.075 −111.553 124.595 1.00 133.20 ATOM 362 N GLY G 128 78.684 −110.063 123.048 1.00 131.94 ATOM 363 CA GLY G 128 78.941 −108.702 122.614 1.00 131.82 ATOM 364 C GLY G 128 80.436 −108.454 122.541 1.00 131.76 ATOM 365 O GLY G 128 81.051 −108.049 123.527 1.00 131.75 ATOM 366 N ALA G 129 81.009 −108.709 121.367 1.00 131.69 ATOM 367 CA ALA G 129 82.439 −108.541 121.102 1.00 131.75 ATOM 368 C ALA G 129 83.240 −107.898 122.232 1.00 132.17 ATOM 369 O ALA G 129 84.144 −108.523 122.787 1.00 132.86 ATOM 370 CB ALA G 129 82.632 −107.748 119.819 1.00 131.22 ATOM 371 N GLY G 130 82.913 −106.649 122.558 1.00 131.78 ATOM 372 CA GLY G 130 83.615 −105.949 123.621 1.00 130.67 ATOM 373 C GLY G 130 84.005 −106.869 124.763 1.00 130.19 ATOM 374 O GLY G 130 83.255 −107.782 125.104 1.00 130.65 ATOM 375 N SER G 195 85.182 −106.632 125.341 1.00 128.61 ATOM 376 CA SER G 195 85.705 −107.429 126.454 1.00 126.30 ATOM 377 C SER G 195 84.590 −108.085 127.275 1.00 125.16 ATOM 378 O SER G 195 83.538 −107.483 127.495 1.00 125.28 ATOM 379 CB SER G 195 86.570 −106.538 127.345 1.00 125.36 ATOM 380 OG SER G 195 87.524 −105.831 126.567 1.00 121.97 ATOM 381 N CYS G 196 84.830 −109.311 127.740 1.00 122.96 ATOM 382 CA CYS G 196 83.821 −110.058 128.490 1.00 120.58 ATOM 383 C CYS G 196 83.992 −110.143 130.010 1.00 118.42 ATOM 384 O CYS G 196 84.973 −109.664 130.580 1.00 117.88 ATOM 385 CB CYS G 196 83.720 −111.480 127.931 1.00 120.97 ATOM 386 SG CYS G 196 84.469 −111.710 126.286 1.00 122.59 ATOM 387 N ASP G 197 83.008 −110.771 130.649 1.00 115.33 ATOM 388 CA ASP G 197 82.992 −110.960 132.095 1.00 112.91 ATOM 389 C ASP G 197 82.935 −112.461 132.366 1.00 111.21 ATOM 390 O ASP G 197 82.951 −113.257 131.431 1.00 111.48 ATOM 391 CB ASP G 197 81.766 −110.273 132.701 1.00 114.40 ATOM 392 CG ASP G 197 81.916 −110.021 134.191 1.00 116.21 ATOM 393 OD1 ASP G 197 82.826 −109.253 134.563 1.00 118.31 ATOM 394 OD2 ASP G 197 81.132 −110.590 134.980 1.00 116.81 ATOM 395 N THR G 198 82.848 −112.849 133.633 1.00 108.94 ATOM 396 CA THR G 198 82.796 −114.265 133.987 1.00 106.71 ATOM 397 C THR G 198 81.395 −114.729 134.392 1.00 104.11 ATOM 398 O THR G 198 80.627 −113.974 134.988 1.00 105.56 ATOM 399 CB THR G 198 83.760 −114.574 135.144 1.00 108.19 ATOM 400 OG1 THR G 198 83.441 −113.738 136.263 1.00 109.13 ATOM 401 CG2 THR G 198 85.190 −114.315 134.729 1.00 108.79 ATOM 402 N SER G 199 81.071 −115.978 134.068 1.00 101.10 ATOM 403 CA SER G 199 79.765 −116.555 134.395 1.00 98.61 ATOM 404 C SER G 199 79.905 −117.657 135.444 1.00 96.43 ATOM 405 O SER G 199 80.584 −118.661 135.216 1.00 96.37 ATOM 406 CB SER G 199 79.113 −117.124 133.130 1.00 98.18 ATOM 407 OG SER G 199 77.821 −117.635 133.406 1.00 96.50 ATOM 408 N VAL G 200 79.247 −117.479 136.584 1.00 92.80 ATOM 409 CA VAL G 200 79.331 −118.454 137.664 1.00 89.88 ATOM 410 C VAL G 200 78.074 −119.310 137.797 1.00 87.32 ATOM 411 O VAL G 200 76.954 −118.798 137.747 1.00 86.48 ATOM 412 CB VAL G 200 79.568 −117.749 139.012 1.00 90.70 ATOM 413 CG1 VAL G 200 80.051 −118.755 140.045 1.00 90.81 ATOM 414 CG2 VAL G 200 80.568 −116.621 138.831 1.00 91.35 ATOM 415 N ILE G 201 78.270 −120.614 137.976 1.00 84.68 ATOM 416 CA ILE G 201 77.164 −121.552 138.132 1.00 81.86 ATOM 417 C ILE G 201 77.483 −122.552 139.234 1.00 79.73 ATOM 418 O ILE G 201 78.516 −123.210 139.197 1.00 79.56 ATOM 419 CB ILE G 201 76.904 −122.366 136.840 1.00 82.08 ATOM 420 CG1 ILE G 201 76.600 −121.432 135.666 1.00 85.27 ATOM 421 CG2 ILE G 201 75.733 −123.311 137.055 1.00 78.87 ATOM 422 CD1 ILE G 201 77.830 −120.796 135.047 1.00 89.69 ATOM 423 N THR G 202 76.600 −122.667 140.216 1.00 78.11 ATOM 424 CA THR G 202 76.812 −123.613 141.299 1.00 79.05 ATOM 425 C THR G 202 75.852 −124.794 141.137 1.00 80.92 ATOM 426 O THR G 202 74.653 −124.609 140.906 1.00 81.00 ATOM 427 CB THR G 202 76.575 −122.964 142.667 1.00 78.00 ATOM 428 OG1 THR G 202 75.243 −122.452 142.725 1.00 79.43 ATOM 429 CG2 THR G 202 77.549 −121.842 142.901 1.00 77.99 ATOM 430 N GLN G 203 76.384 −126.007 141.249 1.00 81.69 ATOM 431 CA GLN G 203 75.571 −127.207 141.104 1.00 81.90 ATOM 432 C GLN G 203 76.077 −128.353 141.977 1.00 83.87 ATOM 433 O GLN G 203 77.208 −128.325 142.457 1.00 84.27 ATOM 434 CB GLN G 203 75.548 −127.628 139.635 1.00 80.36 ATOM 435 CG GLN G 203 76.918 −127.643 138.979 1.00 79.24 ATOM 436 CD GLN G 203 76.859 −128.040 137.514 1.00 80.19 ATOM 437 OE1 GLN G 203 76.167 −127.412 136.714 1.00 79.78 ATOM 438 NE2 GLN G 203 77.589 −129.090 137.157 1.00 80.36 ATOM 439 N ALA G 204 75.232 −129.359 142.181 1.00 86.42 ATOM 440 CA ALA G 204 75.593 −130.514 143.003 1.00 87.19 ATOM 441 C ALA G 204 76.718 −131.315 142.355 1.00 87.49 ATOM 442 O ALA G 204 76.692 −131.563 141.156 1.00 85.76 ATOM 443 CB ALA G 204 74.366 −131.405 143.209 1.00 86.04 ATOM 444 N CYS G 205 77.702 −131.728 143.149 1.00 89.57 ATOM 445 CA CYS G 205 78.808 −132.510 142.609 1.00 93.38 ATOM 446 C CYS G 205 79.087 −133.832 143.328 1.00 96.85 ATOM 447 O CYS G 205 79.822 −133.876 144.314 1.00 96.56 ATOM 448 CB CYS G 205 80.083 −131.668 142.558 1.00 92.11 ATOM 449 SG CYS G 205 80.806 −131.144 144.146 1.00 93.23 ATOM 450 N PRO G 206 78.506 −134.938 142.826 1.00 100.89 ATOM 451 CA PRO G 206 78.691 −136.266 143.416 1.00 105.01 ATOM 452 C PRO G 206 80.095 −136.768 143.099 1.00 109.65 ATOM 453 O PRO G 206 80.606 −136.538 142.004 1.00 110.64 ATOM 454 CB PRO G 206 77.621 −137.107 142.719 1.00 103.87 ATOM 455 CG PRO G 206 76.607 −136.099 142.253 1.00 102.48 ATOM 456 CD PRO G 206 77.497 −135.000 141.757 1.00 102.04 ATOM 457 N LYS G 207 80.719 −137.456 144.044 1.00 114.22 ATOM 458 CA LYS G 207 82.064 −137.960 143.823 1.00 119.19 ATOM 459 C LYS G 207 82.101 −139.371 143.241 1.00 123.01 ATOM 460 O LYS G 207 82.701 −140.267 143.830 1.00 124.82 ATOM 461 CB LYS G 207 82.851 −137.922 145.139 1.00 119.60 ATOM 462 CG LYS G 207 83.462 −136.565 145.466 1.00 119.01 ATOM 463 CD LYS G 207 84.876 −136.473 144.916 1.00 118.82 ATOM 464 CE LYS G 207 85.454 −135.076 145.044 1.00 117.77 ATOM 465 NZ LYS G 207 84.868 −134.134 144.051 1.00 116.94 ATOM 466 N ILE G 208 81.466 −139.574 142.091 1.00 127.08 ATOM 467 CA ILE G 208 81.482 −140.893 141.466 1.00 131.24 ATOM 468 C ILE G 208 82.668 −141.008 140.512 1.00 132.68 ATOM 469 O ILE G 208 83.143 −140.004 139.984 1.00 133.21 ATOM 470 CB ILE G 208 80.184 −141.174 140.682 1.00 132.20 ATOM 471 CG1 ILE G 208 79.995 −140.133 139.584 1.00 132.98 ATOM 472 CG2 ILE G 208 78.995 −141.165 141.622 1.00 132.23 ATOM 473 CD1 ILE G 208 78.847 −140.446 138.655 1.00 134.64 ATOM 474 N SER G 209 83.138 −142.234 140.295 1.00 134.15 ATOM 475 CA SER G 209 84.284 −142.480 139.429 1.00 135.70 ATOM 476 C SER G 209 83.970 −142.546 137.938 1.00 137.12 ATOM 477 O SER G 209 83.009 −143.192 137.517 1.00 138.29 ATOM 478 CB SER G 209 84.979 −143.779 139.850 1.00 134.98 ATOM 479 OG SER G 209 84.086 −144.875 139.771 1.00 135.08 ATOM 480 N PHE G 210 84.798 −141.869 137.146 1.00 137.24 ATOM 481 CA PHE G 210 84.660 −141.858 135.694 1.00 137.12 ATOM 482 C PHE G 210 85.467 −143.033 135.152 1.00 138.23 ATOM 483 O PHE G 210 86.687 −142.950 135.018 1.00 138.35 ATOM 484 CB PHE G 210 85.200 −140.546 135.121 1.00 136.15 ATOM 485 CG PHE G 210 85.309 −140.538 133.623 1.00 135.14 ATOM 486 CD1 PHE G 210 84.170 −140.630 132.828 1.00 134.46 ATOM 487 CD2 PHE G 210 86.550 −140.429 133.003 1.00 134.03 ATOM 488 CE1 PHE G 210 84.266 −140.612 131.436 1.00 133.36 ATOM 489 CE2 PHE G 210 86.657 −140.409 131.614 1.00 133.27 ATOM 490 CZ PHE G 210 85.513 −140.499 130.829 1.00 133.06 ATOM 491 N GLU G 211 84.774 −144.126 134.852 1.00 139.29 ATOM 492 CA GLU G 211 85.408 −145.342 134.347 1.00 140.31 ATOM 493 C GLU G 211 85.710 −145.289 132.849 1.00 140.01 ATOM 494 O GLU G 211 84.856 −144.906 132.049 1.00 139.77 ATOM 495 CB GLU G 211 84.515 −146.543 134.648 1.00 141.10 ATOM 496 CG GLU G 211 84.410 −146.875 136.128 1.00 143.21 ATOM 497 CD GLU G 211 83.070 −147.479 136.492 1.00 144.76 ATOM 498 OE1 GLU G 211 82.970 −148.106 137.568 1.00 145.16 ATOM 499 OE2 GLU G 211 82.114 −147.317 135.704 1.00 146.11 ATOM 500 N PRO G 212 86.933 −145.685 132.452 1.00 139.56 ATOM 501 CA PRO G 212 87.358 −145.686 131.050 1.00 139.07 ATOM 502 C PRO G 212 86.618 −146.766 130.271 1.00 138.18 ATOM 503 O PRO G 212 87.206 −147.771 129.876 1.00 138.23 ATOM 504 CB PRO G 212 88.858 −145.974 131.143 1.00 139.58 ATOM 505 CG PRO G 212 89.224 −145.516 132.532 1.00 139.85 ATOM 506 CD PRO G 212 88.063 −146.041 133.324 1.00 139.87 ATOM 507 N ILE G 213 85.327 −146.555 130.049 1.00 136.58 ATOM 508 CA ILE G 213 84.515 −147.525 129.329 1.00 134.44 ATOM 509 C ILE G 213 84.844 −147.553 127.836 1.00 133.16 ATOM 510 O ILE G 213 84.751 −146.535 127.154 1.00 133.40 ATOM 511 CB ILE G 213 83.025 −147.221 129.538 1.00 134.18 ATOM 512 CG1 ILE G 213 82.170 −148.233 128.780 1.00 133.60 ATOM 513 CG2 ILE G 213 82.728 −145.797 129.093 1.00 134.56 ATOM 514 CD1 ILE G 213 80.713 −148.192 129.175 1.00 134.43 ATOM 515 N PRO G 214 85.234 −148.730 127.316 1.00 131.77 ATOM 516 CA PRO G 214 85.590 −148.929 125.907 1.00 130.01 ATOM 517 C PRO G 214 84.603 −148.292 124.933 1.00 128.02 ATOM 518 O PRO G 214 83.390 −148.418 125.097 1.00 126.87 ATOM 519 CB PRO G 214 85.637 −150.449 125.787 1.00 130.90 ATOM 520 CG PRO G 214 86.169 −150.848 127.130 1.00 131.42 ATOM 521 CD PRO G 214 85.294 −150.012 128.043 1.00 131.68 ATOM 522 N ILE G 215 85.131 −147.609 123.922 1.00 126.22 ATOM 523 CA ILE G 215 84.297 −146.949 122.928 1.00 124.39 ATOM 524 C ILE G 215 84.606 −147.439 121.517 1.00 123.82 ATOM 525 O ILE G 215 85.758 −147.432 121.089 1.00 123.83 ATOM 526 CB ILE G 215 84.498 −145.419 122.972 1.00 124.52 ATOM 527 CG1 ILE G 215 83.798 −144.853 124.204 1.00 124.66 ATOM 528 CG2 ILE G 215 83.946 −144.775 121.712 1.00 123.95 ATOM 529 CD1 ILE G 215 82.301 −145.085 124.207 1.00 126.40 ATOM 530 N HIS G 216 83.567 −147.855 120.801 1.00 122.91 ATOM 531 CA HIS G 216 83.707 −148.337 119.436 1.00 122.26 ATOM 532 C HIS G 216 83.005 −147.378 118.487 1.00 122.82 ATOM 533 O HIS G 216 81.782 −147.263 118.512 1.00 122.59 ATOM 534 CB HIS G 216 83.064 −149.719 119.279 1.00 121.11 ATOM 535 CG HIS G 216 83.602 −150.756 120.212 1.00 120.49 ATOM 536 ND1 HIS G 216 84.919 −151.164 120.198 1.00 120.39 ATOM 537 CD2 HIS G 216 82.988 −151.501 121.161 1.00 120.37 ATOM 538 CE1 HIS G 216 85.091 −152.118 121.096 1.00 120.82 ATOM 539 NE2 HIS G 216 83.935 −152.341 121.694 1.00 120.97 ATOM 540 N TYR G 217 83.767 −146.678 117.657 1.00 124.13 ATOM 541 CA TYR G 217 83.154 −145.780 116.686 1.00 126.48 ATOM 542 C TYR G 217 82.753 −146.675 115.523 1.00 129.20 ATOM 543 O TYR G 217 83.591 −147.022 114.699 1.00 129.59 ATOM 544 CB TYR G 217 84.159 −144.736 116.202 1.00 124.57 ATOM 545 CG TYR G 217 83.551 −143.677 115.308 1.00 123.48 ATOM 546 CD1 TYR G 217 82.990 −142.522 115.849 1.00 123.73 ATOM 547 CD2 TYR G 217 83.531 −143.831 113.921 1.00 123.00 ATOM 548 CE1 TYR G 217 82.427 −141.541 115.033 1.00 123.68 ATOM 549 CE2 TYR G 217 82.969 −142.858 113.096 1.00 123.64 ATOM 550 CZ TYR G 217 82.420 −141.715 113.658 1.00 123.44 ATOM 551 OH TYR G 217 81.865 −140.755 112.843 1.00 122.11 ATOM 552 N CYS G 218 81.486 −147.070 115.462 1.00 132.82 ATOM 553 CA CYS G 218 81.054 −147.947 114.380 1.00 136.36 ATOM 554 C CYS G 218 80.480 −147.158 113.202 1.00 137.85 ATOM 555 O CYS G 218 80.050 −146.011 113.357 1.00 138.46 ATOM 556 CB CYS G 218 79.996 −148.934 114.866 1.00 137.77 ATOM 557 SG CYS G 218 80.410 −149.952 116.317 1.00 141.47 ATOM 558 N ALA G 219 80.464 −147.790 112.031 1.00 138.84 ATOM 559 CA ALA G 219 79.953 −147.180 110.806 1.00 139.87 ATOM 560 C ALA G 219 78.437 −147.322 110.652 1.00 140.76 ATOM 561 O ALA G 219 77.887 −148.416 110.788 1.00 140.94 ATOM 562 CB ALA G 219 80.656 −147.793 109.599 1.00 139.80 ATOM 563 N PRO G 220 77.747 −146.211 110.347 1.00 141.32 ATOM 564 CA PRO G 220 76.292 −146.186 110.168 1.00 142.02 ATOM 565 C PRO G 220 75.880 −146.886 108.878 1.00 142.66 ATOM 566 O PRO G 220 76.725 −147.227 108.052 1.00 143.05 ATOM 567 CB PRO G 220 75.973 −144.688 110.128 1.00 141.53 ATOM 568 CG PRO G 220 77.147 −144.054 110.841 1.00 141.13 ATOM 569 CD PRO G 220 78.287 −144.845 110.277 1.00 140.75 ATOM 570 N ALA G 221 74.580 −147.099 108.708 1.00 143.48 ATOM 571 CA ALA G 221 74.079 −147.743 107.503 1.00 143.71 ATOM 572 C ALA G 221 74.302 −146.806 106.325 1.00 142.82 ATOM 573 O ALA G 221 73.748 −145.708 106.284 1.00 142.96 ATOM 574 CB ALA G 221 72.603 −148.056 107.654 1.00 144.82 ATOM 575 N GLY G 222 75.115 −147.243 105.370 1.00 140.94 ATOM 576 CA GLY G 222 75.396 −146.417 104.209 1.00 138.32 ATOM 577 C GLY G 222 76.792 −145.835 104.279 1.00 136.29 ATOM 578 O GLY G 222 77.201 −145.050 103.424 1.00 136.34 ATOM 579 N PHE G 223 77.526 −146.238 105.311 1.00 134.39 ATOM 580 CA PHE G 223 78.890 −145.777 105.537 1.00 132.34 ATOM 581 C PHE G 223 79.777 −146.927 106.001 1.00 130.44 ATOM 582 O PHE G 223 79.291 −147.921 106.542 1.00 130.04 ATOM 583 CB PHE G 223 78.894 −144.670 106.592 1.00 132.84 ATOM 584 CG PHE G 223 78.252 −143.397 106.134 1.00 133.73 ATOM 585 CD1 PHE G 223 78.935 −142.528 105.292 1.00 133.66 ATOM 586 CD2 PHE G 223 76.967 −143.061 106.547 1.00 134.47 ATOM 587 CE1 PHE G 223 78.352 −141.337 104.868 1.00 134.19 ATOM 588 CE2 PHE G 223 76.371 −141.871 106.128 1.00 135.20 ATOM 589 CZ PHE G 223 77.067 −141.007 105.287 1.00 135.04 ATOM 590 N ALA G 224 81.081 −146.784 105.788 1.00 128.35 ATOM 591 CA ALA G 224 82.038 −147.806 106.189 1.00 126.17 ATOM 592 C ALA G 224 83.350 −147.160 106.618 1.00 124.72 ATOM 593 O ALA G 224 83.741 −146.125 106.083 1.00 124.65 ATOM 594 CB ALA G 224 82.280 −148.763 105.033 1.00 126.68 ATOM 595 N ILE G 225 84.028 −147.771 107.583 1.00 122.82 ATOM 596 CA ILE G 225 85.296 −147.238 108.062 1.00 121.00 ATOM 597 C ILE G 225 86.481 −148.096 107.630 1.00 119.79 ATOM 598 O ILE G 225 86.477 −149.316 107.801 1.00 119.03 ATOM 599 CB ILE G 225 85.293 −147.094 109.603 1.00 121.03 ATOM 600 CG1 ILE G 225 84.767 −148.369 110.258 1.00 120.98 ATOM 601 CG2 ILE G 225 84.438 −145.910 110.010 1.00 120.24 ATOM 602 CD1 ILE G 225 85.843 −149.311 110.722 1.00 120.08 ATOM 603 N LEU G 226 87.488 −147.442 107.061 1.00 118.45 ATOM 604 CA LEU G 226 88.692 −148.108 106.575 1.00 117.87 ATOM 605 C LEU G 226 89.778 −148.170 107.644 1.00 117.93 ATOM 606 O LEU G 226 90.048 −147.181 108.320 1.00 117.78 ATOM 607 CB LEU G 226 89.233 −147.360 105.355 1.00 117.84 ATOM 608 CG LEU G 226 88.416 −147.465 104.067 1.00 117.99 ATOM 609 CD1 LEU G 226 88.412 −146.134 103.329 1.00 117.75 ATOM 610 CD2 LEU G 226 89.000 −148.571 103.202 1.00 118.64 ATOM 611 N LYS G 227 90.405 −149.333 107.784 1.00 118.28 ATOM 612 CA LYS G 227 91.465 −149.518 108.766 1.00 119.16 ATOM 613 C LYS G 227 92.802 −149.761 108.070 1.00 120.69 ATOM 614 O LYS G 227 93.016 −150.822 107.486 1.00 121.36 ATOM 615 CB LYS G 227 91.137 −150.710 109.674 1.00 117.69 ATOM 616 CG LYS G 227 92.124 −150.907 110.812 1.00 116.17 ATOM 617 CD LYS G 227 92.021 −152.297 111.418 1.00 115.50 ATOM 618 CE LYS G 227 93.166 −152.535 112.389 1.00 114.84 ATOM 619 NZ LYS G 227 93.253 −153.948 112.850 1.00 113.75 ATOM 620 N CYS G 228 93.701 −148.782 108.125 1.00 122.52 ATOM 621 CA CYS G 228 95.013 −148.931 107.494 1.00 124.88 ATOM 622 C CYS G 228 95.858 −149.909 108.317 1.00 125.15 ATOM 623 O CYS G 228 96.285 −149.591 109.427 1.00 125.31 ATOM 624 CB CYS G 228 95.704 −147.560 107.380 1.00 127.78 ATOM 625 SG CYS G 228 97.401 −147.576 106.702 1.00 132.08 ATOM 626 N ASN G 229 96.082 −151.103 107.768 1.00 125.50 ATOM 627 CA ASN G 229 96.859 −152.135 108.452 1.00 126.07 ATOM 628 C ASN G 229 98.350 −152.104 108.155 1.00 126.43 ATOM 629 O ASN G 229 99.019 −153.135 108.224 1.00 126.40 ATOM 630 CB ASN G 229 96.331 −153.533 108.114 1.00 127.05 ATOM 631 CG ASN G 229 95.052 −153.874 108.855 1.00 128.07 ATOM 632 OD1 ASN G 229 93.960 −153.472 108.455 1.00 129.09 ATOM 633 ND2 ASN G 229 95.185 −154.612 109.953 1.00 128.62 ATOM 634 N ASP G 230 98.873 −150.931 107.822 1.00 127.09 ATOM 635 CA ASP G 230 100.298 −150.803 107.541 1.00 128.18 ATOM 636 C ASP G 230 101.112 −151.040 108.808 1.00 129.06 ATOM 637 O ASP G 230 100.792 −150.501 109.867 1.00 129.47 ATOM 638 CB ASP G 230 100.611 −149.413 106.994 1.00 128.04 ATOM 639 CG ASP G 230 100.772 −149.400 105.486 1.00 128.21 ATOM 640 OD1 ASP G 230 99.829 −149.813 104.784 1.00 129.16 ATOM 641 OD2 ASP G 230 101.844 −148.972 105.012 1.00 127.80 ATOM 642 N LYS G 231 102.174 −151.832 108.693 1.00 130.19 ATOM 643 CA LYS G 231 103.034 −152.142 109.833 1.00 131.50 ATOM 644 C LYS G 231 103.705 −150.890 110.406 1.00 132.11 ATOM 645 O LYS G 231 103.862 −150.762 111.620 1.00 132.26 ATOM 646 CB LYS G 231 104.103 −153.164 109.420 1.00 131.22 ATOM 647 CG LYS G 231 103.545 −154.525 108.994 1.00 131.29 ATOM 648 CD LYS G 231 102.981 −155.296 110.185 1.00 131.06 ATOM 649 CE LYS G 231 102.249 −156.559 109.747 1.00 130.17 ATOM 650 NZ LYS G 231 101.640 −157.279 110.904 1.00 128.78 ATOM 651 N THR G 232 104.100 −149.970 109.531 1.00 132.72 ATOM 652 CA THR G 232 104.750 −148.738 109.960 1.00 133.16 ATOM 653 C THR G 232 104.170 −147.577 109.173 1.00 133.64 ATOM 654 O THR G 232 104.627 −147.283 108.072 1.00 134.29 ATOM 655 CB THR G 232 106.264 −148.791 109.698 1.00 133.30 ATOM 656 OG1 THR G 232 106.807 −149.976 110.286 1.00 133.19 ATOM 657 CG2 THR G 232 106.956 −147.583 110.304 1.00 134.01 ATOM 658 N PHE G 233 103.162 −146.923 109.741 1.00 133.70 ATOM 659 CA PHE G 233 102.506 −145.798 109.086 1.00 134.07 ATOM 660 C PHE G 233 102.979 −144.482 109.689 1.00 133.22 ATOM 661 O PHE G 233 103.185 −144.394 110.897 1.00 133.97 ATOM 662 CB PHE G 233 100.990 −145.927 109.240 1.00 135.95 ATOM 663 CG PHE G 233 100.211 −145.067 108.293 1.00 138.56 ATOM 664 CD1 PHE G 233 100.413 −145.170 106.922 1.00 139.24 ATOM 665 CD2 PHE G 233 99.267 −144.163 108.766 1.00 139.44 ATOM 666 CE1 PHE G 233 99.687 −144.386 106.031 1.00 140.27 ATOM 667 CE2 PHE G 233 98.534 −143.372 107.885 1.00 140.80 ATOM 668 CZ PHE G 233 98.744 −143.485 106.513 1.00 140.90 ATOM 669 N ASN G 234 103.137 −143.455 108.857 1.00 132.11 ATOM 670 CA ASN G 234 103.606 −142.163 109.353 1.00 131.12 ATOM 671 C ASN G 234 102.497 −141.209 109.789 1.00 130.16 ATOM 672 O ASN G 234 102.776 −140.083 110.195 1.00 130.18 ATOM 673 CB ASN G 234 104.479 −141.463 108.305 1.00 131.40 ATOM 674 CG ASN G 234 103.667 −140.844 107.184 1.00 131.18 ATOM 675 OD1 ASN G 234 103.832 −139.666 106.859 1.00 130.27 ATOM 676 ND2 ASN G 234 102.791 −141.636 106.581 1.00 130.32 ATOM 677 N GLY G 235 101.246 −141.649 109.711 1.00 128.79 ATOM 678 CA GLY G 235 100.152 −140.784 110.119 1.00 127.79 ATOM 679 C GLY G 235 99.372 −140.177 108.967 1.00 127.12 ATOM 680 O GLY G 235 98.186 −140.456 108.808 1.00 126.69 ATOM 681 N LYS G 236 100.023 −139.334 108.171 1.00 126.63 ATOM 682 CA LYS G 236 99.361 −138.704 107.031 1.00 126.89 ATOM 683 C LYS G 236 100.036 −139.113 105.726 1.00 128.87 ATOM 684 O LYS G 236 101.238 −239.357 105.693 1.00 129.74 ATOM 685 CB LYS G 236 99.386 −137.177 107.169 1.00 124.81 ATOM 686 CG LYS G 236 100.774 −136.597 107.412 1.00 122.07 ATOM 687 CD LYS G 236 100.770 −135.068 107.512 1.00 120.19 ATOM 688 CE LYS G 236 100.766 −134.390 106.146 1.00 118.90 ATOM 689 NZ LYS G 236 100.848 −132.901 106.254 1.00 116.47 ATOM 690 N GLY G 237 99.254 −139.183 104.654 1.00 130.44 ATOM 691 CA GLY G 237 99.797 −139.569 103.364 1.00 132.18 ATOM 692 C GLY G 237 99.066 −140.755 102.767 1.00 133.46 ATOM 693 O GLY G 237 97.921 −141.018 103.138 1.00 134.02 ATOM 694 N PRO G 238 99.693 −141.487 101.838 1.00 133.68 ATOM 695 CA PRO G 238 99.075 −142.651 101.200 1.00 133.81 ATOM 696 C PRO G 238 99.297 −143.951 101.985 1.00 133.94 ATOM 697 O PRO G 238 100.427 −144.267 102.353 1.00 133.93 ATOM 698 CB PRO G 238 99.759 −142.702 99.827 1.00 133.77 ATOM 699 CG PRO G 238 100.463 −141.336 99.685 1.00 134.36 ATOM 700 CD PRO G 238 100.886 −141.069 101.093 1.00 134.13 ATOM 701 N CYS G 239 98.228 −144.703 102.245 1.00 134.81 ATOM 702 CA CYS G 239 98.361 −145.976 102.959 1.00 136.32 ATOM 703 C CYS G 239 98.399 −147.104 101.926 1.00 136.72 ATOM 704 O CYS G 239 97.640 −147.086 100.958 1.00 136.38 ATOM 705 CB CYS G 239 97.187 −146.196 103.935 1.00 136.44 ATOM 706 SG CYS G 239 97.192 −147.860 104.696 1.00 136.59 ATOM 707 N LYS G 240 99.274 −148.086 102.136 1.00 138.05 ATOM 708 CA LYS G 240 99.405 −149.212 101.207 1.00 139.87 ATOM 709 C LYS G 240 98.342 −150.286 101.428 1.00 139.47 ATOM 710 O LYS G 240 97.436 −150.447 100.613 1.00 139.04 ATOM 711 CB LYS G 240 100.802 −149.837 101.324 1.00 141.13 ATOM 712 CG LYS G 240 101.941 −148.901 100.918 1.00 142.81 ATOM 713 CD LYS G 240 103.310 −149.526 101.173 1.00 143.74 ATOM 714 CE LYS G 240 104.429 −148.549 100.835 1.00 143.78 ATOM 715 NZ LYS G 240 105.786 −149.103 101.110 1.00 143.33 ATOM 716 N ASN G 241 98.458 −151.020 102.530 1.00 139.54 ATOM 717 CA ASN G 241 97.499 −152.070 102.850 1.00 139.69 ATOM 718 C ASN G 241 96.445 −151.535 103.811 1.00 139.92 ATOM 719 O ASN G 241 96.774 −151.092 104.908 1.00 139.69 ATOM 720 CB ASN G 241 98.207 −153.257 103.505 1.00 139.80 ATOM 721 CG ASN G 241 97.305 −154.468 103.640 1.00 140.13 ATOM 722 OD1 ASN G 241 97.503 −155.314 104.512 1.00 139.63 ATOM 723 ND2 ASN G 241 96.312 −154.563 102.763 1.00 139.93 ATOM 724 N VAL G 242 95.182 −151.588 103.405 1.00 139.96 ATOM 725 CA VAL G 242 94.098 −151.102 104.249 1.00 140.28 ATOM 726 C VAL G 242 92.840 −151.950 104.097 1.00 140.63 ATOM 727 O VAL G 242 92.326 −152.114 102.991 1.00 141.19 ATOM 728 CB VAL G 242 93.759 −149.631 103.905 1.00 140.31 ATOM 729 CG1 VAL G 242 93.609 −149.479 102.400 1.00 139.72 ATOM 730 CG2 VAL G 242 92.476 −149.210 104.607 1.00 140.48 ATOM 731 N SER G 243 92.350 −152.486 105.211 1.00 140.58 ATOM 732 CA SER G 243 91.149 −153.322 105.211 1.00 140.55 ATOM 733 C SER G 243 89.925 −152.489 105.588 1.00 140.69 ATOM 734 O SER G 243 90.002 −151.264 105.656 1.00 140.64 ATOM 735 CB SER G 243 91.308 −154.467 106.213 1.00 140.83 ATOM 736 OG SER G 243 91.381 −153.972 107.536 1.00 140.52 ATOM 737 N THR G 244 88.804 −153.157 105.845 1.00 141.03 ATOM 738 CA THR G 244 87.582 −152.460 106.212 1.00 141.52 ATOM 739 C THR G 244 86.765 −153.217 107.244 1.00 142.08 ATOM 740 O THR G 244 86.149 −154.231 106.927 1.00 141.97 ATOM 741 CB THR G 244 86.683 −152.231 104.983 1.00 141.57 ATOM 742 OG1 THR G 244 87.375 −151.421 104.032 1.00 142.02 ATOM 743 CG2 THR G 244 85.395 −151.532 105.384 1.00 140.17 ATOM 744 N VAL G 245 86.769 −152.726 108.476 1.00 142.71 ATOM 745 CA VAL G 245 86.005 −153.338 109.549 1.00 143.44 ATOM 746 C VAL G 245 84.747 −152.503 109.763 1.00 143.75 ATOM 747 O VAL G 245 84.627 −151.413 109.204 1.00 143.15 ATOM 748 CB VAL G 245 86.821 −153.377 110.853 1.00 144.12 ATOM 749 CG1 VAL G 245 87.881 −154.460 110.778 1.00 144.77 ATOM 750 CG2 VAL G 245 87.479 −152.032 111.086 1.00 144.53 ATOM 751 N GLN G 246 83.808 −153.006 110.557 1.00 144.36 ATOM 752 CA GLN G 246 82.577 −152.266 110.799 1.00 144.77 ATOM 753 C GLN G 246 82.652 −151.364 112.024 1.00 144.15 ATOM 754 O GLN G 246 82.087 −150.272 112.025 1.00 143.24 ATOM 755 CB GLN G 246 81.392 −153.227 110.918 1.00 146.20 ATOM 756 CG GLN G 246 81.220 −154.117 109.699 1.00 148.95 ATOM 757 CD GLN G 246 81.195 −153.327 108.400 1.00 150.00 ATOM 758 OE1 GLN G 246 80.344 −152.461 108.202 1.00 150.67 ATOM 759 NE2 GLN G 246 82.136 −153.623 107.510 1.00 149.89 ATOM 760 N CYS G 247 83.338 −151.814 113.069 1.00 143.81 ATOM 761 CA CYS G 247 83.474 −150.999 114.274 1.00 143.17 ATOM 762 C CYS G 247 84.949 −150.785 114.595 1.00 142.65 ATOM 763 O CYS G 247 85.796 −151.613 114.255 1.00 142.71 ATOM 764 CB CYS G 247 82.810 −151.662 115.485 1.00 142.99 ATOM 765 SG CYS G 247 80.988 −151.740 115.542 1.00 143.43 ATOM 766 N THR G 248 85.247 −149.676 115.262 1.00 141.73 ATOM 767 CA THR G 248 86.613 −149.336 115.640 1.00 140.76 ATOM 768 C THR G 248 87.070 −150.095 116.883 1.00 140.31 ATOM 769 O THR G 248 86.258 −150.456 117.731 1.00 140.20 ATOM 770 CB THR G 248 86.725 −147.838 115.923 1.00 140.39 ATOM 771 OG1 THR G 248 86.168 −147.112 114.824 1.00 141.14 ATOM 772 CG2 THR G 248 88.169 −147.433 116.094 1.00 140.10 ATOM 773 N HIS G 249 88.375 −150.325 116.991 1.00 139.86 ATOM 774 CA HIS G 249 88.932 −151.035 118.138 1.00 139.38 ATOM 775 C HIS G 249 88.597 −150.355 119.464 1.00 137.88 ATOM 776 O HIS G 249 88.282 −149.167 119.501 1.00 138.46 ATOM 777 CB HIS G 249 90.449 −151.170 117.990 1.00 140.83 ATOM 778 CG HIS G 249 90.872 −152.257 117.049 1.00 143.17 ATOM 779 ND1 HIS G 249 90.448 −152.316 115.739 1.00 143.35 ATOM 780 CD2 HIS G 249 91.689 −153.323 117.227 1.00 143.40 ATOM 781 CE1 HIS G 249 90.986 −153.371 115.151 1.00 143.13 ATOM 782 NE2 HIS G 249 91.743 −153.998 116.032 1.00 143.09 ATOM 783 N GLY G 250 88.672 −151.119 120.550 1.00 135.79 ATOM 784 CA GLY G 250 88.359 −150.585 121.865 1.00 132.31 ATOM 785 C GLY G 250 89.255 −149.450 122.328 1.00 129.65 ATOM 786 O GLY G 250 90.404 −149.674 122.714 1.00 129.34 ATOM 787 N ILE G 251 88.723 −148.232 122.302 1.00 126.82 ATOM 788 CA ILE G 251 89.464 −147.053 122.729 1.00 123.65 ATOM 789 C ILE G 251 89.083 −146.696 124.159 1.00 121.43 ATOM 790 O ILE G 251 87.906 −146.528 124.468 1.00 121.14 ATOM 791 CB ILE G 251 89.145 −145.841 121.836 1.00 123.65 ATOM 792 CG1 ILE G 251 89.420 −146.199 120.375 1.00 124.47 ATOM 793 CG2 ILE G 252 89.983 −144.643 122.259 1.00 122.65 ATOM 794 CD1 ILE G 251 90.843 −146.656 120.116 1.00 125.76 ATOM 795 N ARG G 252 90.082 −146.581 125.025 1.00 119.23 ATOM 796 CA ARG G 252 89.857 −146.237 126.422 1.00 117.32 ATOM 797 C ARG G 252 89.886 −144.713 126.553 1.00 114.89 ATOM 798 O ARG G 252 90.918 −144.088 126.322 1.00 114.47 ATOM 799 CB ARG G 252 90.959 −146.854 127.291 1.00 119.04 ATOM 800 CG ARG G 252 91.398 −148.252 126.860 1.00 120.89 ATOM 801 CD ARG G 252 90.441 −149.350 127.320 1.00 123.64 ATOM 802 NE ARG G 252 90.658 −149.735 128.715 1.00 125.39 ATOM 803 CZ ARG G 252 90.032 −150.741 129.319 1.00 125.75 ATOM 804 NH1 ARG G 252 89.145 −151.468 128.653 1.00 126.03 ATOM 805 NH2 ARG G 252 90.296 −151.025 130.589 1.00 124.96 ATOM 806 N PRO G 253 88.749 −144.093 126.923 1.00 113.15 ATOM 807 CA PRO G 253 88.674 −142.635 127.073 1.00 112.07 ATOM 808 C PRO G 253 89.467 −142.080 128.254 1.00 111.17 ATOM 809 O PRO G 253 88.925 −141.891 129.346 1.00 111.86 ATOM 810 CB PRO G 253 87.178 −142.389 127.228 1.00 111.80 ATOM 811 CG PRO G 253 86.754 −143.589 128.011 1.00 112.54 ATOM 812 CD PRO G 253 87.441 −144.700 127.232 1.00 113.08 ATOM 813 N VAL G 254 90.746 −141.807 128.022 1.00 109.24 ATOM 814 CA VAL G 254 91.622 −141.274 129.057 1.00 106.74 ATOM 815 C VAL G 254 92.049 −139.851 128.722 1.00 106.15 ATOM 816 O VAL G 254 92.714 −139.615 127.712 1.00 105.35 ATOM 817 CB VAL G 254 92.894 −142.136 129.198 1.00 106.43 ATOM 818 CG1 VAL G 254 93.815 −141.539 130.252 1.00 105.45 ATOM 819 CG2 VAL G 254 92.516 −143.559 129.568 1.00 105.32 ATOM 820 N VAL G 255 91.659 −138.906 129.567 1.00 105.48 ATOM 821 CA VAL G 255 92.020 −137.511 129.363 1.00 104.38 ATOM 822 C VAL G 255 93.205 −137.137 130.244 1.00 102.82 ATOM 823 O VAL G 255 93.042 −136.827 131.423 1.00 103.17 ATOM 824 CB VAL G 255 90.835 −136.573 129.684 1.00 103.63 ATOM 825 CG1 VAL G 255 89.960 −136.398 128.452 1.00 102.60 ATOM 826 CG2 VAL G 255 90.013 −137.153 130.821 1.00 103.74 ATOM 827 N SER G 256 94.399 −137.177 129.664 1.00 101.35 ATOM 828 CA SER G 256 95.619 −136.849 130.391 1.00 100.45 ATOM 829 C SER G 256 96.587 −136.050 129.530 1.00 99.76 ATOM 830 O SER G 256 96.492 −136.053 128.304 1.00 99.01 ATOM 831 CB SER G 256 96.298 −138.133 130.875 1.00 100.56 ATOM 832 OG SER G 256 96.534 −139.020 129.799 1.00 100.95 ATOM 833 N THR G 257 97.529 −135.379 130.182 1.00 99.86 ATOM 834 CA THR G 257 98.513 −134.566 129.479 1.00 100.65 ATOM 835 C THR G 257 99.914 −135.174 129.524 1.00 101.63 ATOM 836 O THR G 257 100.217 −136.011 130.380 1.00 101.64 ATOM 837 CB THR G 257 98.581 −133.145 130.078 1.00 99.95 ATOM 838 OG1 THR G 257 98.775 −133.230 131.496 1.00 97.28 ATOM 839 CG2 THR G 257 97.307 −132.392 129.795 1.00 100.77 ATOM 840 N GLN G 258 100.762 −134.744 128.591 1.00 101.38 ATOM 841 CA GLN G 258 102.140 −135.218 128.506 1.00 101.30 ATOM 842 C GLN G 258 102.259 −136.706 128.194 1.00 101.52 ATOM 843 O GLN G 258 102.841 −137.083 127.180 1.00 101.61 ATOM 844 CB GLN G 258 102.879 −134.899 129.807 1.00 102.03 ATOM 845 CG GLN G 258 102.869 −133.420 130.152 1.00 104.23 ATOM 846 CD GLN G 258 103.675 −133.098 131.394 1.00 105.40 ATOM 847 OE1 GLN G 258 103.500 −133.721 132.440 1.00 106.32 ATOM 848 NE2 GLN G 258 104.560 −132.114 131.286 1.00 107.50 ATOM 849 N LEU G 259 101.713 −137.546 129.068 1.00 101.69 ATOM 850 CA LEU G 259 101.768 −138.993 128.881 1.00 102.17 ATOM 851 C LEU G 259 100.423 −139.538 128.414 1.00 102.41 ATOM 852 O LEU G 259 99.373 −139.022 128.788 1.00 102.52 ATOM 853 CB LEU G 259 102.160 −139.681 130.196 1.00 101.92 ATOM 854 CG LEU G 259 103.530 −139.358 130.810 1.00 101.73 ATOM 855 CD1 LEU G 259 103.500 −139.663 132.298 1.00 99.97 ATOM 856 CD2 LEU G 259 104.617 −140.161 130.111 1.00 101.60 ATOM 857 N LEU G 260 100.465 −140.582 127.593 1.00 102.49 ATOM 858 CA LEU G 260 99.251 −141.217 127.088 1.00 102.67 ATOM 859 C LEU G 260 99.110 −142.568 127.778 1.00 103.61 ATOM 860 O LEU G 260 99.966 −143.437 127.621 1.00 103.69 ATOM 861 CB LEU G 260 99.353 −141.409 125.576 1.00 101.68 ATOM 862 CG LEU G 260 99.448 −140.122 124.752 1.00 101.95 ATOM 863 CD1 LEU G 260 99.953 −140.434 123.355 1.00 104.05 ATOM 864 CD2 LEU G 260 98.086 −139.457 124.703 1.00 102.22 ATOM 865 N LEU G 261 98.030 −142.748 128.533 1.00 105.17 ATOM 866 CA LEU G 261 97.815 −143.991 129.276 1.00 106.41 ATOM 867 C LEU G 261 96.661 −144.836 128.744 1.00 107.21 ATOM 868 O LEU G 261 95.708 −144.314 128.167 1.00 106.94 ATOM 869 CB LEU G 261 97.549 −143.661 130.743 1.00 105.72 ATOM 870 CG LEU G 261 98.232 −142.392 131.272 1.00 104.79 ATOM 871 CD1 LEU G 261 97.660 −142.057 132.637 1.00 105.02 ATOM 872 CD2 LEU G 261 99.741 −142.577 131.340 1.00 103.55 ATOM 873 N ASN G 262 96.752 −146.147 128.959 1.00 108.66 ATOM 874 CA ASN G 262 95.724 −147.091 128.515 1.00 110.01 ATOM 875 C ASN G 262 95.280 −146.877 127.074 1.00 112.35 ATOM 876 O ASN G 262 94.183 −146.376 126.822 1.00 113.39 ATOM 877 CB ASN G 262 94.502 −147.021 129.432 1.00 108.26 ATOM 878 CG ASN G 262 94.817 −147.452 130.846 1.00 107.34 ATOM 879 OD1 ASN G 262 95.692 −148.294 131.054 1.00 106.57 ATOM 880 ND2 ASN G 262 94.093 −146.901 131.819 1.00 107.98 ATOM 881 N GLY G 263 96.129 −147.276 126.132 1.00 114.75 ATOM 882 CA GLY G 263 95.801 −147.115 124.728 1.00 117.52 ATOM 883 C GLY G 263 96.326 −148.237 123.856 1.00 119.64 ATOM 884 O GLY G 263 96.747 −149.284 124.354 1.00 119.72 ATOM 885 N SER G 264 96.308 −148.008 122.547 1.00 121.07 ATOM 886 CA SER G 264 96.771 −148.992 121.578 1.00 122.04 ATOM 887 C SER G 264 98.291 −149.038 121.482 1.00 123.78 ATOM 888 O SER G 264 98.949 −148.003 121.362 1.00 123.31 ATOM 889 CB SER G 264 96.178 −148.678 120.201 1.00 120.42 ATOM 890 OG SER G 264 96.593 −149.632 119.242 1.00 120.43 ATOM 891 N LEU G 265 98.844 −150.244 121.540 1.00 126.40 ATOM 892 CA LEU G 265 100.286 −150.421 121.448 1.00 129.15 ATOM 893 C LEU G 265 100.693 −150.823 120.037 1.00 130.72 ATOM 894 O LEU G 265 99.983 −151.573 119.368 1.00 130.95 ATOM 895 CB LEU G 265 100.764 −151.493 122.433 1.00 130.79 ATOM 896 CG LEU G 265 100.641 −151.191 123.929 1.00 132.07 ATOM 897 CD1 LEU G 265 99.572 −152.079 124.562 1.00 132.65 ATOM 898 CD2 LEU G 265 101.988 −151.433 124.590 1.00 131.38 ATOM 899 N ALA G 266 101.838 −150.322 119.586 1.00 132.23 ATOM 900 CA ALA G 266 102.339 −150.651 118.259 1.00 134.12 ATOM 901 C ALA G 266 102.910 −152.065 118.269 1.00 135.84 ATOM 902 O ALA G 266 103.783 −152.381 119.077 1.00 136.72 ATOM 903 CB ALA G 266 103.413 −149.656 117.848 1.00 133.87 ATOM 904 N GLU G 267 102.417 −152.911 117.370 1.00 137.31 ATOM 905 CA GLU G 267 102.878 −154.294 117.286 1.00 138.28 ATOM 906 C GLU G 267 104.287 −154.420 116.704 1.00 138.43 ATOM 907 O GLU G 267 104.941 −155.449 116.877 1.00 138.51 ATOM 908 CB GLU G 267 101.913 −155.128 116.435 1.00 139.08 ATOM 909 CG GLU G 267 101.055 −156.140 117.199 1.00 140.98 ATOM 910 CD GLU G 267 100.029 −155.491 118.109 1.00 142.29 ATOM 911 OE1 GLU G 267 100.397 −155.083 119:230 1.00 143.33 ATOM 912 OE2 GLU G 267 98.855 −155.381 117.696 1.00 142.39 ATOM 913 N GLU G 268 104.752 −153.384 116.011 1.00 138.17 ATOM 914 CA GLU G 268 106.084 −153.414 115.408 1.00 137.57 ATOM 915 C GLU G 268 107.102 −152.595 116.197 1.00 136.57 ATOM 916 O GLU G 268 107.669 −153.080 117.175 1.00 135.78 ATOM 917 CB GLU G 268 106.017 −152.915 113.959 1.00 137.43 ATOM 918 CG GLU G 268 105.211 −153.810 113.019 1.00 137.50 ATOM 919 CD GLU G 268 105.925 −155.107 112.673 1.00 136.95 ATOM 920 OE1 GLU G 268 106.938 −155.053 111.943 1.00 136.48 ATOM 921 OE2 GLU G 268 105.474 −156.178 113.133 1.00 135.94 ATOM 922 N GLU G 269 107.332 −151.358 115.767 1.00 136.24 ATOM 923 CA GLU G 269 108.289 −150.478 116.434 1.00 135.49 ATOM 924 C GLU G 269 107.654 −149.157 116.855 1.00 134.06 ATOM 925 O GLU G 269 106.488 −148.888 116.558 1.00 133.72 ATOM 926 CB GLU G 269 109.470 −150.193 115.500 1.00 136.19 ATOM 927 CG GLU G 269 110.272 −151.422 115.099 1.00 136.58 ATOM 928 CD GLU G 269 111.252 −151.862 116.170 1.00 136.55 ATOM 929 OE1 GLU G 269 112.182 −151.086 116.479 1.00 136.08 ATOM 930 OE2 GLU G 269 111.095 −152.982 116.700 1.00 136.04 ATOM 931 N VAL G 270 108.431 −148.335 117.553 1.00 132.32 ATOM 932 CA VAL G 270 107.958 −147.031 117.994 1.00 130.76 ATOM 933 C VAL G 270 107.775 −146.124 116.783 1.00 129.81 ATOM 934 O VAL G 270 108.685 −145.973 115.968 1.00 130.00 ATOM 935 CB VAL G 270 108.966 −146.377 118.966 1.00 131.35 ATOM 936 CG1 VAL O 270 108.937 −144.860 118.811 1.00 131.66 ATOM 937 CG2 VAL G 270 108.621 −146.755 120.395 1.00 130.81 ATOM 938 N VAL G 271 106.598 −145.520 116.668 1.00 128.20 ATOM 939 CA VAL G 271 106.313 −144.636 115.547 1.00 126.00 ATOM 940 C VAL G 271 105.937 −143.226 115.975 1.00 123.76 ATOM 941 O VAL G 271 104.888 −143.009 116.581 1.00 123.89 ATOM 942 CB VAL G 271 105.168 −145.198 114.680 1.00 127.31 ATOM 943 CG1 VAL G 271 105.713 −146.225 113.699 1.00 127.47 ATOM 944 CG2 VAL G 271 104.117 −145.838 115.573 1.00 128.06 ATOM 945 N ILE G 272 106.804 −142.272 115.656 1.00 121.03 ATOM 946 CA ILE G 272 106.572 −140.872 115.990 1.00 118.57 ATOM 947 C ILE G 272 105.975 −140.139 114.795 1.00 116.72 ATOM 948 O ILE G 272 106.352 −140.394 113.652 1.00 116.74 ATOM 949 CB ILE G 272 107.887 −140.177 116.415 1.00 118.70 ATOM 950 CG1 ILE G 272 109.042 −140.617 115.512 1.00 119.92 ATOM 951 CG2 ILE G 272 108.203 −140.507 117.860 1.00 118.21 ATOM 952 CD1 ILE G 272 109.082 −139.944 114.157 1.00 120.90 ATOM 953 N ARG G 273 105.040 −139.232 115.052 1.00 114.52 ATOM 954 CA ARG G 273 104.405 −138.500 113.967 1.00 112.62 ATOM 955 C ARG G 273 103.923 −137.100 114.334 1.00 112.88 ATOM 956 O ARG G 273 103.487 −136.845 115.455 1.00 113.04 ATOM 957 CB ARG G 273 103.254 −139.339 113.401 1.00 110.31 ATOM 958 CG ARG G 273 102.587 −140.260 114.417 1.00 106.44 ATOM 959 CD ARG G 273 102.311 −141.625 113.795 1.00 104.49 ATOM 960 NE ARG G 273 101.683 −142.560 114.726 1.00 102.80 ATOM 961 CZ ARG G 273 101.400 −143.826 114.433 1.00 101.53 ATOM 962 NH1 ARG G 273 101.691 −144.310 113.234 1.00 99.91 ATOM 963 NH2 ARG G 273 100.825 −144.607 115.337 1.00 100.38 ATOM 964 N SER G 274 104.018 −136.199 113.363 1.00 113.32 ATOM 965 CA SER G 274 103.618 −134.810 113.531 1.00 114.33 ATOM 966 C SER G 274 103.131 −134.296 112.184 1.00 115.69 ATOM 967 O SER G 274 103.519 −134.816 111.140 1.00 115.97 ATOM 968 CB SER G 274 104.814 −133.974 114.003 1.00 114.12 ATOM 969 OG SER G 274 104.457 −132.617 114.198 1.00 114.92 ATOM 970 N ASP G 275 102.285 −133.274 112.205 1.00 117.50 ATOM 971 CA ASP G 275 101.764 −132.718 110.966 1.00 119.82 ATOM 972 C ASP G 275 102.906 −132.161 110.109 1.00 122.54 ATOM 973 O ASP G 275 102.898 −132.283 108.885 1.00 123.77 ATOM 974 CB ASP G 275 100.742 −131.626 111.284 1.00 119.48 ATOM 975 CG ASP G 275 99.978 −131.168 110.059 1.00 119.15 ATOM 976 OD1 ASP G 275 100.457 −130.241 109.380 1.00 119.47 ATOM 977 OD2 ASP G 275 98.907 −131.748 109.774 1.00 119.52 ATOM 978 N ASN G 276 103.885 −131.547 110.766 1.00 124.54 ATOM 979 CA ASN G 276 105.053 −130.984 110.095 1.00 126.17 ATOM 980 C ASN G 276 106.182 −130.957 111.116 1.00 126.16 ATOM 981 O ASN G 276 106.209 −130.097 111.996 1.00 127.07 ATOM 982 CB ASN G 276 104.764 −129.565 109.575 1.00 127.69 ATOM 983 CG ASN G 276 105.951 −128.957 108.826 1.00 130.48 ATOM 984 OD1 ASN G 276 106.983 −128.684 109.436 1.00 131.45 ATOM 985 ND2 ASN G 276 105.817 −128.752 107.512 1.00 133.41 ATOM 986 N PHE G 277 107.098 −131.915 111.001 1.00 125.51 ATOM 987 CA PHE G 277 108.223 −132.013 111.917 1.00 124.73 ATOM 988 C PHE G 277 109.164 −130.820 111.885 1.00 124.32 ATOM 989 O PHE G 277 109.851 −130.543 112.869 1.00 124.52 ATOM 990 CB PHE G 277 109.021 −133.282 111.645 1.00 124.97 ATOM 991 CG PHE G 277 108.616 −134.440 112.498 1.00 124.70 ATOM 992 CD1 PHE G 277 107.662 −135.352 112.061 1.00 124.33 ATOM 993 CD2 PHE G 277 109.177 −134.606 113.758 1.00 125.19 ATOM 994 CE1 PHE G 277 107.274 −136.416 112.872 1.00 124.54 ATOM 995 CE2 PHE G 277 108.797 −135.661 114.575 1.00 125.18 ATOM 996 CZ PHE G 277 107.843 −136.568 114.132 1.00 124.26 ATOM 997 N THR G 278 109.205 −130.113 110.763 1.00 123.74 ATOM 998 CA THR G 278 110.082 −126.954 110.660 1.00 123.33 ATOM 999 C THR G 278 109.545 −127.821 111.522 1.00 122.48 ATOM 1000 O THR G 278 110.298 −126.961 111.974 1.00 122.37 ATOM 1001 CB THR G 278 110.194 −128.471 109.208 1.00 123.77 ATOM 1002 OG1 THR G 278 110.512 −129.583 108.363 1.00 122.39 ATOM 1003 CG2 THR G 278 111.299 −127.432 109.076 1.00 124.71 ATOM 1004 N ASN G 279 108.237 −127.836 111.752 1.00 121.41 ATOM 1005 CA ASN G 279 107.588 −126.823 112.569 1.00 120.64 ATOM 1006 C ASN G 279 107.553 −127.290 114.019 1.00 119.86 ATOM 1007 O ASN G 279 107.075 −128.384 114.316 1.00 119.77 ATOM 1008 CB ASN G 279 106.168 −126.570 112.060 1.00 122.36 ATOM 1009 CG ASN G 279 105.527 −125.362 112.703 1.00 123.19 ATOM 1010 OD1 ASN G 279 106.104 −124.276 112.716 1.00 124.95 ATOM 1011 ND2 ASN G 279 104.322 −125.540 113.228 1.00 123.66 ATOM 1012 N ASN G 280 108.059 −126.451 114.917 1.00 118.87 ATOM 1013 CA ASN G 280 108.107 −126.780 116.336 1.00 118.01 ATOM 1014 C ASN G 280 106.785 −126.592 117.075 1.00 117.08 ATOM 1015 O ASN G 280 106.615 −127.104 118.181 1.00 117.55 ATOM 1016 CB ASN G 280 109.187 −125.943 117.019 1.00 118.90 ATOM 1017 CG ASN G 280 109.006 −124.457 116.781 1.00 119.84 ATOM 1018 OD1 ASN G 280 108.992 −124.001 115.638 1.00 119.58 ATOM 1019 ND2 ASN G 280 108.865 −123.694 117.859 1.00 121.00 ATOM 1020 N ALA G 281 105.851 −125.862 116.472 1.00 115.19 ATOM 1021 CA ALA G 281 104.557 −125.612 117.102 1.00 112.13 ATOM 1022 C ALA G 281 103.663 −126.842 117.077 1.00 109.69 ATOM 1023 O ALA G 281 102.802 −127.010 117.937 1.00 109.86 ATOM 1024 CB ALA G 281 103.859 −124.453 116.409 1.00 113.29 ATOM 1025 N LYS G 282 103.865 −127.693 116.078 1.00 106.77 ATOM 1026 CA LYS G 282 103.078 −128.911 115.939 1.00 104.34 ATOM 1027 C LYS G 282 103.510 −129.937 116.979 1.00 102.27 ATOM 1028 O LYS G 282 104.699 −130.197 117.147 1.00 101.74 ATOM 1029 CB LYS G 282 103.260 −129.495 114.534 1.00 104.78 ATOM 1030 CG LYS G 282 102.841 −128.579 113.392 1.00 105.16 ATOM 1031 CD LYS G 282 101.326 −128.507 113.226 1.00 107.10 ATOM 1032 CE LYS G 282 100.956 −127.757 111.947 1.00 107.70 ATOM 1033 NZ LYS G 282 99.493 −127.777 111.657 1.00 108.40 ATOM 1034 N THR G 283 102.542 −130.523 117.671 1.00 100.94 ATOM 1035 CA THR G 283 102.848 −131.514 118.693 1.00 100.59 ATOM 1036 C THR G 283 103.256 −132.850 118.076 1.00 99.16 ATOM 1037 O THR G 283 102.777 −133.227 117.003 1.00 98.27 ATOM 1038 CB THR G 283 101.643 −131.751 119.620 1.00 102.18 ATOM 1039 OG1 THR G 283 100.523 −132.185 118.843 1.00 103.66 ATOM 1040 CG2 THR G 283 101.276 −130.478 120.352 1.00 102.55 ATOM 1041 N ILE G 284 104.135 −133.567 118.767 1.00 97.96 ATOM 1042 CA ILE G 284 104.616 −134.855 118.292 1.00 97.14 ATOM 1043 C ILE G 284 104.064 −136.005 119.123 1.00 97.31 ATOM 1044 O ILE G 284 104.344 −136.110 120.318 1.00 97.07 ATOM 1045 CB ILE G 284 106.157 −134.899 118.331 1.00 96.52 ATOM 1046 CG1 ILE G 284 106.714 −133.841 117.375 1.00 96.20 ATOM 1047 CG2 ILE G 284 106.656 −136.293 117.964 1.00 96.59 ATOM 1048 CD1 ILE G 284 108.195 −133.608 117.509 1.00 96.44 ATOM 1049 N ILE G 285 103.276 −136.863 118.485 1.00 98.01 ATOM 1050 CA ILE G 285 102.685 −138.013 119.158 1.00 99.80 ATOM 1051 C ILE G 285 103.602 −139.229 119.071 1.00 101.17 ATOM 1052 O ILE G 285 103.975 −139.661 117.980 1.00 100.52 ATOM 1053 CB ILE G 285 101.312 −138.386 118.537 1.00 99.80 ATOM 1054 CG1 ILE G 285 100.246 −137.372 118.961 1.00 100.25 ATOM 1055 CG2 ILE G 285 100.903 −139.782 118.977 1.00 100.16 ATOM 1056 CD1 ILE G 285 100.455 −135.980 118.409 1.00 102.53 ATOM 1057 N VAL G 286 103.955 −139.782 120.224 1.00 103.62 ATOM 1058 CA VAL G 286 104.831 −140.943 120.282 1.00 106.86 ATOM 1059 C VAL G 286 104.055 −142.192 120.683 1.00 109.26 ATOM 1060 O VAL G 286 103.311 −142.176 121.663 1.00 109.45 ATOM 1061 CB VAL G 286 105.953 −140.727 121.314 1.00 107.59 ATOM 1062 CG1 VAL G 286 106.960 −141.865 121.236 1.00 108.43 ATOM 1063 CG2 VAL G 286 106.621 −139.385 121.074 1.00 107.25 ATOM 1064 N GLN G 287 104.222 −143.270 119.923 1.00 112.10 ATOM 1065 CA GLN G 287 103.540 −144.527 120.225 1.00 115.20 ATOM 1066 C GLN G 287 104.575 −145.549 120.675 1.00 116.64 ATOM 1067 O GLN G 287 105.564 −145.779 119.982 1.00 117.12 ATOM 1068 CB GLN G 287 102.803 −145.057 118.992 1.00 116.06 ATOM 1069 CG GLN G 287 101.378 −145.514 119.275 1.00 117.17 ATOM 1070 CD GLN G 287 100.932 −146.653 118.378 1.00 117.46 ATOM 1071 OE1 GLN G 287 101.086 −146.600 117.158 1.00 116.74 ATOM 1072 NE2 GLN G 287 100.366 −147.692 118.984 1.00 117.73 ATOM 1073 N LEU G 288 104.338 −146.170 121.825 1.00 119.08 ATOM 1074 CA LEU G 288 105.270 −147.150 122.375 1.00 122.20 ATOM 1075 C LEU G 288 104.788 −148.588 122.203 1.00 124.20 ATOM 1076 O LEU G 288 103.594 −148.867 122.309 1.00 124.85 ATOM 1077 CB LEU G 288 105.479 −146.874 123.862 1.00 121.50 ATOM 1078 CG LEU G 288 105.844 −145.433 124.231 1.00 121.43 ATOM 1079 CD1 LEU G 288 105.637 −145.233 125.720 1.00 122.39 ATOM 1080 CD2 LEU G 288 107.281 −145.134 123.832 1.00 123.19 ATOM 1081 N LYS G 289 105.721 −149.503 121.953 1.00 126.07 ATOM 1082 CA LYS G 289 105.380 −150.912 121.782 1.00 127.42 ATOM 1083 C LYS G 289 105.478 −151.682 123.097 1.00 127.68 ATOM 1084 O LYS G 289 104.856 −152.732 123.258 1.00 126.88 ATOM 1085 CB LYS G 289 106.285 −151.552 120.723 1.00 128.03 ATOM 1086 CG LYS G 289 107.441 −150.673 120.252 1.00 129.35 ATOM 1087 CD LYS G 289 108.782 −151.209 120.736 1.00 130.44 ATOM 1088 CE LYS G 289 109.966 −150.519 120.051 1.00 130.23 ATOM 1089 NZ LYS G 289 110.464 −149.301 120.754 1.00 131.22 ATOM 1090 N GLU G 290 106.263 −151.159 124.033 1.00 128.43 ATOM 1091 CA GLU G 290 106.416 −151.788 125.341 1.00 128.96 ATOM 1092 C GLU G 290 105.619 −150.998 126.375 1.00 127.87 ATOM 1093 O GLU G 290 105.837 −149.800 126.553 1.00 127.30 ATOM 1094 CB GLU G 290 107.894 −151.843 125.744 1.00 131.22 ATOM 1095 CG GLU G 290 108.714 −152.872 124.974 1.00 134.12 ATOM 1096 CD GLU G 290 110.117 −153.047 125.532 1.00 135.56 ATOM 1097 OE1 GLU G 290 110.924 −152.097 125.442 1.00 136.25 ATOM 1098 OE2 GLU G 290 110.412 −154.138 126.064 1.00 135.63 ATOM 1099 N SER G 291 104.697 −151.673 127.052 1.00 126.04 ATOM 1100 CA SER G 291 103.856 −151.030 128.053 1.00 124.60 ATOM 1101 C SER G 291 104.589 −150.693 129.344 1.00 124.35 ATOM 1102 O SER G 291 105.113 −151.577 130.025 1.00 125.69 ATOM 1103 CB SER G 291 102.656 −151.922 128.379 1.00 123.78 ATOM 1104 OG SER G 291 103.084 −153.161 128.915 1.00 123.88 ATOM 1105 N VAL G 292 104.615 −149.408 129.679 1.00 123.16 ATOM 1106 CA VAL G 292 105.263 −148.941 130.898 1.00 121.87 ATOM 1107 C VAL G 292 104.192 −148.750 131.968 1.00 121.23 ATOM 1108 O VAL G 292 103.399 −147.813 131.897 1.00 120.89 ATOM 1109 CB VAL G 292 105.968 −147.595 130.662 1.00 121.78 ATOM 1110 CG1 VAL G 292 106.742 −147.191 131.907 1.00 121.71 ATOM 1111 CG2 VAL G 292 106.886 −147.697 129.461 1.00 120.71 ATOM 1112 N GLU G 293 104.169 −149.640 132.952 1.00 120.89 ATOM 1113 CA GLU G 293 103.178 −149.574 134.015 1.00 121.29 ATOM 1114 C GLU G 293 103.474 −148.476 135.031 1.00 121.55 ATOM 1115 O GLU G 293 104.568 −148.408 135.591 1.00 121.80 ATOM 1116 CB GLU G 293 103.086 −150.933 134.723 1.00 121.08 ATOM 1117 CG GLU G 293 102.116 −150.988 135.893 1.00 121.19 ATOM 1118 CD GLU G 293 101.966 −152.394 136.445 1.00 122.13 ATOM 1119 OE1 GLU G 293 102.946 −153.167 136.371 1.00 122.07 ATOM 1120 OE2 GLU G 293 100.876 −152.722 136.961 1.00 123.25 ATOM 1121 N ILE G 294 102.493 −147.610 135.258 1.00 121.87 ATOM 1122 CA ILE G 294 102.637 −146.524 136.217 1.00 121.70 ATOM 1123 C ILE G 294 101.621 −146.720 137.333 1.00 121.42 ATOM 1124 O ILE G 294 100.433 −146.917 137.076 1.00 121.27 ATOM 1125 CB ILE G 294 102.418 −145.160 135.536 1.00 122.02 ATOM 1126 CG1 ILE G 294 102.578 −144.033 136.557 1.00 122.87 ATOM 1127 CG2 ILE G 294 101.048 −145.125 134.884 1.00 121.44 ATOM 1128 CD1 ILE G 294 102.714 −142.660 135.931 1.00 122.60 ATOM 1129 N ASN G 295 102.097 −146.674 138.573 1.00 121.00 ATOM 1130 CA ASN G 295 101.238 −146.874 139.736 1.00 121.44 ATOM 1131 C ASN G 295 101.204 −145.674 140.677 1.00 121.01 ATOM 1132 O ASN G 295 102.134 −145.462 141.457 1.00 121.03 ATOM 1133 CB ASN G 295 101.710 −148.103 140.517 1.00 122.74 ATOM 1134 CG ASN G 295 101.810 −149.344 139.651 1.00 122.92 ATOM 1135 OD1 ASN G 295 100.819 −149.793 139.075 1.00 122.88 ATOM 1136 ND2 ASN G 295 103.011 −149.905 139.555 1.00 122.92 ATOM 1137 N CYS G 296 100.124 −144.901 140.605 1.00 120.25 ATOM 1138 CA CYS G 296 99.960 −143.728 141.456 1.00 118.86 ATOM 1139 C CYS G 296 98.928 −144.045 142.537 1.00 117.99 ATOM 1140 O CYS G 296 97.835 −144.528 142.236 1.00 117.00 ATOM 1141 CB CYS G 296 99.466 −142.537 140.636 1.00 119.34 ATOM 1142 SG CYS G 296 100.316 −142.227 139.052 1.00 119.64 ATOM 1143 N THR G 297 99.268 −143.765 143.791 1.00 117.75 ATOM 1144 CA THR G 297 98.356 −144.042 144.895 1.00 117.96 ATOM 1145 C THR G 297 98.386 −142.956 145.967 1.00 117.03 ATOM 1146 O THR G 297 99.224 −142.055 145.933 1.00 115.96 ATOM 1147 CB THR G 297 98.692 −145.394 145.560 1.00 118.94 ATOM 1148 OG1 THR G 297 99.992 −145.325 146.159 1.00 120.18 ATOM 1149 CG2 THR G 297 98.688 −146.509 144.524 1.00 119.76 ATOM 1150 N ARG G 298 97.459 −143.050 146.916 1.00 116.66 ATOM 1151 CA ARG G 298 97.369 −142.092 148.010 1.00 116.73 ATOM 1152 C ARG G 298 96.753 −142.780 149.228 1.00 118.95 ATOM 1153 O ARG G 298 95.710 −143.426 149.124 1.00 118.61 ATOM 1154 CB ARG G 298 96.521 −140.888 147.585 1.00 114.49 ATOM 1155 CG ARG G 298 96.550 −139.720 148.564 1.00 112.45 ATOM 1156 CD ARG G 298 95.473 −139.831 149.632 1.00 110.20 ATOM 1157 NE ARG G 298 94.138 −139.603 149.085 1.00 108.71 ATOM 1158 CZ ARG G 298 93.026 −139.566 149.812 1.00 107.87 ATOM 1159 NH1 ARG G 298 93.082 −139.742 151.125 1.00 107.98 ATOM 1160 NH2 ARG G 298 91.857 −139.349 149.227 1.00 107.62 ATOM 1161 N PRO G 299 97.402 −142.651 150.399 1.00 121.18 ATOM 1162 CA PRO G 299 96.984 −143.233 151.681 1.00 123.48 ATOM 1163 C PRO G 299 95.484 −143.182 151.977 1.00 125.98 ATOM 1164 O PRO G 299 94.700 −142.658 151.186 1.00 126.15 ATOM 1165 CB PRO G 299 97.805 −142.442 152.691 1.00 123.50 ATOM 1166 CG PRO G 299 99.092 −142.253 151.958 1.00 122.94 ATOM 1167 CD PRO G 299 98.621 −141.841 150.576 1.00 121.50 ATOM 1168 N ASN G 300 95.092 −143.724 153.127 1.00 127.96 ATOM 1169 CA ASN G 300 93.684 −143.752 153.502 1.00 130.21 ATOM 1170 C ASN G 300 93.364 −143.237 154.905 1.00 131.51 ATOM 1171 O ASN G 300 93.985 −142.292 155.394 1.00 131.18 ATOM 1172 CB ASN G 300 93.137 −145.173 153.341 1.00 130.07 ATOM 1173 CG ASN G 300 93.919 −146.194 154.142 1.00 130.57 ATOM 1174 OD1 ASN G 300 95.139 −146.299 154.015 1.00 130.10 ATOM 1175 ND2 ASN G 300 93.216 −146.958 154.969 1.00 131.18 ATOM 1176 N GLN G 301 92.384 −143.877 155.537 1.00 133.80 ATOM 1177 CA GLN G 301 91.912 −143.514 156.871 1.00 135.82 ATOM 1178 C GLN G 301 92.716 −144.156 158.004 1.00 137.01 ATOM 1179 O GLN G 301 92.448 −143.903 159.180 1.00 136.35 ATOM 1180 CB GLN G 301 90.436 −143.911 157.001 1.00 135.35 ATOM 1181 CG GLN G 301 89.724 −143.404 158.248 1.00 135.28 ATOM 1182 CD GLN G 301 89.563 −141.897 158.258 1.00 134.83 ATOM 1183 OE1 GLN G 301 89.785 −141.230 157.247 1.00 134.19 ATOM 1184 NE2 GLN G 301 89.160 −141.353 159.402 1.00 133.96 ATOM 1185 N ASN G 302 93.701 −144.979 157.656 1.00 138.83 ATOM 1186 CA ASN G 302 94.522 −145.651 158.662 1.00 140.81 ATOM 1187 C ASN G 302 95.302 −144.706 159.574 1.00 141.45 ATOM 1188 O ASN G 302 96.112 −145.155 160.387 1.00 141.13 ATOM 1189 CB ASN G 302 95.494 −146.633 157.997 1.00 141.80 ATOM 1190 CG ASN G 302 94.851 −147.975 157.690 1.00 143.04 ATOM 1191 OD1 ASN G 302 94.307 −148.632 158.579 1.00 142.23 ATOM 1192 ND2 ASN G 302 94.919 −148.392 156.431 1.00 142.70 ATOM 1193 N THR G 303 95.063 −143.404 159.440 1.00 142.24 ATOM 1194 CA THR G 303 95.745 −142.423 160.278 1.00 142.95 ATOM 1195 C THR G 303 95.430 −142.755 161.734 1.00 143.18 ATOM 1196 O THR G 303 96.274 −143.285 162.457 1.00 143.28 ATOM 1197 CB THR G 303 95.263 −140.990 159.969 1.00 143.28 ATOM 1198 OG1 THR G 303 95.502 −140.691 158.588 1.00 143.23 ATOM 1199 CG2 THR G 303 96.006 −139.980 160.831 1.00 144.01 ATOM 1200 N ARG G 304 94.208 −142.441 162.154 1.00 143.39 ATOM 1201 CA ARG G 304 93.762 −142.731 163.512 1.00 143.68 ATOM 1202 C ARG G 304 92.770 −143.886 163.431 1.00 143.18 ATOM 1203 O ARG G 304 92.051 −144.019 162.441 1.00 143.86 ATOM 1204 CB ARG G 304 93.108 −141.495 164.138 1.00 144.11 ATOM 1205 CG ARG G 304 94.084 −140.349 164.381 1.00 145.32 ATOM 1206 CD ARG G 304 95.261 −140.809 165.238 1.00 147.31 ATOM 1207 NE ARG G 304 96.271 −139.770 165.421 1.00 147.56 ATOM 1208 CZ ARG G 304 97.419 −139.953 166.067 1.00 147.68 ATOM 1209 NH1 ARG G 304 97.706 −141.136 166.593 1.00 146.72 ATOM 1210 NH2 ARG G 304 98.283 −138.953 166.187 1.00 146.63 ATOM 1211 N LYS G 305 92.728 −144.722 164.464 1.00 141.97 ATOM 1212 CA LYS G 305 91.836 −145.874 164.442 1.00 140.98 ATOM 1213 C LYS G 305 90.851 −145.964 165.606 1.00 140.38 ATOM 1214 O LYS G 305 89.921 −146.771 165.565 1.00 140.91 ATOM 1215 CB LYS G 305 92.668 −147.159 164.384 1.00 141.00 ATOM 1216 CG LYS G 305 91.930 −148.361 163.818 1.00 140.99 ATOM 1217 CD LYS G 305 91.633 −148.169 162.338 1.00 141.06 ATOM 1218 CE LYS G 305 90.967 −149.397 161.741 1.00 141.85 ATOM 1219 NZ LYS G 305 90.730 −149.243 160.279 1.00 140.37 ATOM 1220 N SER G 306 91.042 −145.149 166.638 1.00 139.15 ATOM 1221 CA SER G 306 90.143 −145.193 167.788 1.00 137.47 ATOM 1222 C SER G 306 89.922 −143.845 168.466 1.00 136.43 ATOM 1223 O SER G 306 90.820 −143.005 168.518 1.00 136.13 ATOM 1224 CB SER G 306 90.663 −146.198 168.818 1.00 137.39 ATOM 1225 OG SER G 306 90.732 −147.502 168.267 1.00 136.71 ATOM 1226 N ILE G 307 88.713 −143.654 168.985 1.00 135.40 ATOM 1227 CA ILE G 307 88.345 −142.424 169.678 1.00 135.12 ATOM 1228 C ILE G 307 87.998 −142.771 171.124 1.00 133.50 ATOM 1229 O ILE G 307 87.697 −143.924 171.433 1.00 133.64 ATOM 1230 CB ILE G 307 87.122 −141.754 169.013 1.00 135.24 ATOM 1231 CG1 ILE G 307 87.410 −141.505 167.531 1.00 136.04 ATOM 1232 CG2 ILE G 307 86.802 −140.437 169.709 1.00 135.56 ATOM 1233 CD1 ILE G 307 86.248 −140.899 166.770 1.00 137.26 ATOM 1234 N HIS G 308 88.042 −141.777 172.005 1.00 132.91 ATOM 1235 CA HIS G 308 87.739 −141.997 173.416 1.00 132.86 ATOM 1236 C HIS G 308 86.709 −141.003 173.946 1.00 130.36 ATOM 1237 O HIS G 308 86.915 −139.791 173.887 1.00 130.34 ATOM 1238 CB HIS G 308 89.023 −141.899 174.244 1.00 133.35 ATOM 1239 CG HIS G 308 90.081 −142.878 173.836 1.00 134.57 ATOM 1240 ND1 HIS G 308 90.588 −142.935 172.557 1.00 135.10 ATOM 1241 CD2 HIS G 308 90.726 −143.837 174.541 1.00 134.82 ATOM 1242 CE1 HIS G 308 91.501 −143.889 172.490 1.00 135.21 ATOM 1243 NE2 HIS G 308 91.604 −144.451 173.680 1.00 134.93 ATOM 1244 N ILE G 309 85.593 −141.524 174.451 1.00 129.66 ATOM 1245 CA ILE G 309 84.535 −140.678 174.996 1.00 132.96 ATOM 1246 C ILE G 309 84.853 −140.335 176.442 1.00 129.06 ATOM 1247 O ILE G 309 85.368 −141.163 177.189 1.00 130.20 ATOM 1248 CB ILE G 309 83.150 −141.381 174.982 1.00 129.80 ATOM 1249 CG1 ILE G 309 82.794 −141.842 173.567 1.00 129.99 ATOM 1250 CG2 ILE G 309 82.079 −140.427 175.513 1.00 129.45 ATOM 1251 CD1 ILE G 309 82.707 −140.721 172.551 1.00 131.16 ATOM 1252 N AGLY G 312 84.519 −139.106 176.817 0.50 130.34 ATOM 1253 N BGLY G 312 84.580 −139.093 176.821 0.50 130.54 ATOM 1254 CA AGLY G 312 84.745 −138.635 178.168 0.50 130.62 ATOM 1255 CA BGLY G 312 84.870 −138.668 178.175 0.50 132.03 ATOM 1256 C AGLY G 312 83.667 −137.629 178.521 0.50 130.49 ATOM 1257 C BGLY G 312 84.057 −137.472 178.615 0.50 132.56 ATOM 1258 O AGLY G 312 83.395 −136.719 177.734 0.50 129.55 ATOM 1259 O BGLY G 312 83.971 −136.469 177.901 0.50 132.01 ATOM 1260 N APRO G 313 83.028 −137.767 179.695 0.50 130.44 ATOM 1261 N BPRO G 313 83.443 −137.553 179.805 0.50 133.04 ATOM 1262 CA APRO G 313 81.972 −136.840 180.115 0.50 131.53 ATOM 1263 CA BPRO G 313 82.628 −136.463 180.344 0.50 134.04 ATOM 1264 C APRO G 313 82.413 −135.375 180.098 0.50 132.66 ATOM 1265 C BPRO G 313 83.434 −135.170 180.483 0.50 134.58 ATOM 1266 O APRO G 313 81.581 −134.468 180.030 0.50 132.16 ATOM 1267 O BPRO G 313 84.184 −134.985 181.445 0.50 133.93 ATOM 1268 CB APRO G 313 81.618 −137.333 181.522 0.50 130.68 ATOM 1269 CB BPRO G 313 82.148 −137.021 181.686 0.50 133.44 ATOM 1270 CG APRO G 313 82.890 −137.969 181.999 0.50 130.40 ATOM 1271 CG BPRO G 313 83.237 −137.955 182.081 0.50 133.35 ATOM 1272 CD APRO G 313 83.349 −138.718 180.774 0.50 130.35 ATOM 1273 CD BPRO G 313 83.569 −138.649 180.783 0.50 133.12 ATOM 1274 N AGLY G 314 83.726 −135.158 180.147 0.50 133.78 ATOM 1275 N BGLY G 314 83.279 −134.282 179.508 0.50 135.23 ATOM 1276 CA AGLY G 314 84.259 −133.808 180.140 0.50 135.11 ATOM 1277 CA BGLY G 314 84.005 −133.028 179.539 0.50 136.68 ATOM 1278 C AGLY G 314 85.185 −133.514 178.973 0.50 136.46 ATOM 1279 C BGLY G 314 85.217 −133.071 178.633 0.50 137.64 ATOM 1280 O AGLY G 314 85.779 −132.436 178.916 0.50 136.65 ATOM 1281 O BGLY G 314 86.040 −132.151 178.641 0.50 137.68 ATOM 1282 N AARG G 315 85.317 −134.464 178.047 0.50 137.71 ATOM 1283 N BARG G 315 85.330 −134.146 177.855 0.50 138.87 ATOM 1284 CA AARG G 315 86.179 −134.280 176.881 0.50 138.32 ATOM 1285 CA BARG G 315 86.445 −134.302 176.934 0.50 139.12 ATOM 1286 C AARG G 315 86.103 −135.394 175.835 0.50 139.46 ATOM 1287 C BARG G 315 86.339 −135.478 175.969 0.50 140.02 ATOM 1288 O AARG G 315 85.308 −136.326 175.960 0.50 140.02 ATOM 1289 O BARG G 315 85.746 −136.513 176.268 0.50 140.48 ATOM 1290 CB AARG G 315 87.634 −134.069 177.327 0.50 138.97 ATOM 1291 CB BARG G 315 87.766 −134.388 177.707 0.50 140.03 ATOM 1292 CG AARG G 315 88.095 −134.926 178.501 0.50 138.68 ATOM 1293 CG BARG G 315 87.860 −135.517 178.714 0.50 140.27 ATOM 1294 CD AARG G 315 89.381 −134.354 179.103 0.50 138.38 ATOM 1295 CD BARG G 315 89.207 −135.465 179.420 0.50 140.88 ATOM 1296 NE AARG G 315 89.824 −135.078 180.294 0.50 138.70 ATOM 1297 NE BARG G 315 89.349 −136.496 180.445 0.50 140.22 ATOM 1298 CZ AARG G 315 90.845 −134.703 181.062 0.50 138.42 ATOM 1299 CZ BARG G 315 90.422 −136.637 181.219 0.50 139.80 ATOM 1300 NH1 AARG G 315 91.530 −133.607 180.768 0.50 138.28 ATOM 1301 NH1 BARG G 315 91.454 −135.813 181.085 0.50 138.98 ATOM 1302 NH2 AARG G 315 91.181 −135.424 182.125 0.50 138.35 ATOM 1303 NH2 BARG G 315 90.466 −137.604 182.126 0.50 138.56 ATOM 1304 N ALA G 316 86.934 −135.273 174.800 1.00 144.80 ATOM 1305 CA ALA G 316 86.989 −136.226 173.690 1.00 143.79 ATOM 1306 C ALA G 316 88.432 −136.339 173.191 1.00 146.46 ATOM 1307 O ALA G 316 89.285 −135.522 173.549 1.00 147.07 ATOM 1308 CB ALA G 316 86.065 −135.774 172.553 1.00 144.31 ATOM 1309 N PHE G 317 88.701 −137.350 172.366 1.00 149.66 ATOM 1310 CA PHE G 317 90.048 −137.578 171.852 1.00 151.88 ATOM 1311 C PHE G 317 90.071 −137.825 170.343 1.00 152.98 ATOM 1312 O PHE G 317 89.095 −138.305 169.765 1.00 153.44 ATOM 1313 CB PHE G 317 90.693 −138.774 172.565 1.00 151.95 ATOM 1314 CG PHE G 317 90.978 −138.541 174.025 1.00 152.25 ATOM 1315 CD1 PHE G 317 89.940 −138.387 174.940 1.00 151.95 ATOM 1316 CD2 PHE G 317 92.290 −138.486 174.487 1.00 152.28 ATOM 1317 CE1 PHE G 317 90.204 −138.181 176.293 1.00 151.79 ATOM 1318 CE2 PHE G 317 92.565 −138.281 175.838 1.00 152.38 ATOM 1319 CZ PHE G 317 91.519 −138.129 176.742 1.00 152.23 ATOM 1320 N TYR G 318 91.199 −137.492 169.720 1.00 154.53 ATOM 1321 CA TYR G 318 91.406 −137.676 168.283 1.00 155.71 ATOM 1322 C TYR G 318 90.427 −136.911 167.391 1.00 155.64 ATOM 1323 O TYR G 318 89.646 −137.520 166.659 1.00 155.52 ATOM 1324 CB TYR G 318 91.340 −139.165 167.919 1.00 156.48 ATOM 1325 CG TYR G 318 92.267 −140.063 168.711 1.00 157.82 ATOM 1326 CD1 TYR G 318 92.044 −140.309 170.065 1.00 158.34 ATOM 1327 CD2 TYR G 318 93.353 −140.689 168.099 1.00 158.59 ATOM 1328 CE1 TYR G 318 92.875 −141.159 170.791 1.00 158.85 ATOM 1329 CE2 TYR G 318 94.192 −141.542 168.817 1.00 159.15 ATOM 1330 CZ TYR G 318 93.945 −141.772 170.162 1.00 159.22 ATOM 1331 OH TYR G 318 94.765 −142.615 170.877 1.00 159.77 ATOM 1332 N THR G 319 90.474 −135.583 167.440 1.00 155.30 ATOM 1333 CA THR G 319 89.589 −134.763 166.616 1.00 155.09 ATOM 1334 C THR G 319 90.251 −133.430 166.269 1.00 154.62 ATOM 1335 O THR G 319 89.683 −132.611 165.545 1.00 153.91 ATOM 1336 CB THR G 319 88.246 −134.485 167.334 1.00 155.83 ATOM 1337 OG1 THR G 319 87.669 −135.722 167.771 1.00 156.26 ATOM 1338 CG2 THR G 319 87.265 −133.797 166.389 1.00 155.64 ATOM 1339 N THR G 320 91.460 −133.223 166.783 1.00 154.50 ATOM 1340 CA THR G 320 92.199 −131.990 166.532 1.00 154.03 ATOM 1341 C THR G 320 93.278 −132.162 165.463 1.00 153.67 ATOM 1342 O THR G 320 94.420 −131.734 165.646 1.00 153.56 ATOM 1343 CB THR G 320 92.867 −131.467 167.823 1.00 154.73 ATOM 1344 OG1 THR G 320 93.762 −132.462 168.338 1.00 154.90 ATOM 1345 CG2 THR G 320 91.814 −131.143 168.874 1.00 154.48 ATOM 1346 N GLY G 321 92.912 −132.791 164.350 1.00 152.75 ATOM 1347 CA GLY G 321 93.861 −132.995 163.270 1.00 151.08 ATOM 1348 C GLY G 321 94.014 −131.729 162.449 1.00 150.38 ATOM 1349 O GLY G 321 93.119 −131.365 161.685 1.00 149.77 ATOM 1350 N GLU G 322 95.150 −131.056 162.605 1.00 149.39 ATOM 1351 CA GLU G 322 95.405 −129.814 161.884 1.00 148.29 ATOM 1352 C GLU G 322 96.649 −129.909 161.008 1.00 147.73 ATOM 1353 O GLU G 322 96.564 −130.249 159.827 1.00 146.53 ATOM 1354 CB GLU G 322 95.572 −128.662 162.877 1.00 148.27 ATOM 1355 CG GLU G 322 94.503 −128.616 163.956 1.00 148.79 ATOM 1356 CD GLU G 322 94.707 −127.471 164.928 1.00 148.76 ATOM 1357 OE1 GLU G 322 95.819 −127.354 165.485 1.00 148.26 ATOM 1358 OE2 GLU G 322 93.753 −126.693 165.138 1.00 148.68 ATOM 1359 N ILE G 322A 97.801 −129.607 161.603 1.00 147.61 ATOM 1360 CA ILE G 322A 99.087 −129.634 160.910 1.00 147.08 ATOM 1361 C ILE G 322A 98.968 −129.223 159.444 1.00 146.30 ATOM 1362 O ILE G 322A 98.978 −130.067 158.548 1.00 145.89 ATOM 1363 CB ILE G 322A 99.755 −131.036 161.003 1.00 147.76 ATOM 1364 CG1 ILE G 322A 98.807 −132.120 160.480 1.00 148.35 ATOM 1365 CG2 ILE G 322A 100.149 −131.324 162.446 1.00 147.20 ATOM 1366 CD1 ILE G 322A 99.408 −133.513 160.469 1.00 146.09 ATOM 1367 N ILE G 323 98.854 −127.917 159.214 1.00 145.42 ATOM 1368 CA ILE G 323 98.728 −127.370 157.865 1.00 144.18 ATOM 1369 C ILE G 323 99.759 −127.991 156.928 1.00 143.58 ATOM 1370 O ILE G 323 100.878 −127.492 156.799 1.00 143.84 ATOM 1371 CB ILE G 323 98.919 −125.833 157.864 1.00 143.68 ATOM 1372 CG1 ILE G 323 97.919 −125.179 158.823 1.00 142.95 ATOM 1373 CG2 ILE G 323 98.743 −125.285 156.452 1.00 142.76 ATOM 1374 CD1 ILE G 323 96.462 −125.431 158.476 1.00 141.08 ATOM 1375 N GLY G 324 99.371 −129.082 156.275 1.00 142.21 ATOM 1376 CA GLY G 324 100.273 −129.759 155.363 1.00 139.77 ATOM 1377 C GLY G 324 99.607 −130.172 154.067 1.00 137.92 ATOM 1378 O GLY G 324 98.645 −129.543 153.622 1.00 137.70 ATOM 1379 N ASP G 325 100.119 −131.238 153.461 1.00 136.00 ATOM 1380 CA ASP G 325 99.579 −131.735 152.203 1.00 133.50 ATOM 1381 C ASP G 325 98.873 −133.076 152.378 1.00 131.01 ATOM 1382 O ASP G 325 99.517 −134.125 152.420 1.00 130.01 ATOM 1383 CB ASP G 325 100.701 −131.883 151.168 1.00 134.89 ATOM 1384 CG ASP G 325 101.463 −130.587 150.937 1.00 135.71 ATOM 1385 OD1 ASP G 325 100.829 −129.577 150.563 1.00 136.06 ATOM 1386 OD2 ASP G 325 102.698 −130.580 151.125 1.00 134.58 ATOM 1387 N ILE G 326 97.549 −133.035 152.488 1.00 129.15 ATOM 1388 CA ILE G 326 96.752 −134.248 152.636 1.00 127.17 ATOM 1389 C ILE G 326 96.181 −134.612 151.270 1.00 125.06 ATOM 1390 O ILE G 326 95.556 −135.660 151.097 1.00 123.58 ATOM 1391 CB ILE G 326 95.585 −134.060 153.642 1.00 128.41 ATOM 1392 CG1 ILE G 326 94.645 −132.942 153.173 1.00 129.82 ATOM 1393 CG2 ILE G 326 96.140 −133.766 155.028 1.00 127.42 ATOM 1394 CD1 ILE G 326 95.235 −131.542 153.236 1.00 130.42 ATOM 1395 N ARG G 327 96.405 −133.725 150.305 1.00 123.14 ATOM 1396 CA ARG G 327 95.941 −133.924 148.939 1.00 121.11 ATOM 1397 C ARG G 327 97.147 −134.327 148.100 1.00 120.61 ATOM 1398 O ARG G 327 97.188 −134.076 146.897 1.00 120.79 ATOM 1399 CB ARG G 327 95.358 −132.627 148.372 1.00 120.85 ATOM 1400 CG ARG G 327 94.459 −131.843 149.317 1.00 118.55 ATOM 1401 CD ARG G 327 93.929 −130.592 148.622 1.00 116.19 ATOM 1402 NE ARG G 327 93.320 −129.641 149.549 1.00 114.20 ATOM 1403 CZ ARG G 327 92.253 −129.896 150.299 1.00 112.97 ATOM 1404 NH1 ARG G 327 91.661 −131.080 150.241 1.00 112.39 ATOM 1405 NH2 ARG G 327 91.777 −128.963 151.111 1.00 111.25 ATOM 1406 N GLN G 328 98.134 −134.943 148.743 1.00 120.56 ATOM 1407 CA GLN G 328 99.349 −135.363 148.056 1.00 120.47 ATOM 1408 C GLN G 328 99.300 −136.818 147.602 1.00 120.52 ATOM 1409 O GLN G 328 98.731 −137.676 148.278 1.00 119.31 ATOM 1410 CB GLN G 328 100.564 −135.158 148.965 1.00 120.86 ATOM 1411 CG GLN G 328 101.888 −135.560 148.330 1.00 121.32 ATOM 1412 CD GLN G 328 103.053 −135.494 149.302 1.00 121.93 ATOM 1413 OE1 GLN G 328 104.192 −135.792 148.942 1.00 121.20 ATOM 1414 NE2 GLN G 328 102.771 −135.104 150.541 1.00 121.27 ATOM 1415 N ALA G 329 99.909 −137.081 146.451 1.00 120.97 ATOM 1416 CA ALA G 329 99.961 −138.422 145.883 1.00 121.52 ATOM 1417 C ALA G 329 101.311 −138.622 145.204 1.00 122.43 ATOM 1418 O ALA G 329 102.079 −137.673 145.043 1.00 122.38 ATOM 1419 CB ALA G 329 98.836 −138.606 144.877 1.00 121.15 ATOM 1420 N HIS G 330 101.600 −139.858 144.811 1.00 123.54 ATOM 1421 CA HIS G 330 102.861 −140.168 144.150 1.00 124.36 ATOM 1422 C HIS G 330 102.701 −141.357 143.210 1.00 124.92 ATOM 1423 O HIS G 330 101.851 −142.221 143.431 1.00 124.23 ATOM 1424 CB HIS G 330 103.943 −140.473 145.189 1.00 124.54 ATOM 1425 CG HIS G 330 103.653 −141.680 146.028 1.00 125.33 ATOM 1426 ND1 HIS G 330 102.556 −141.764 146.858 1.00 125.66 ATOM 1427 CD2 HIS G 330 104.317 −142.852 146.162 1.00 125.46 ATOM 1428 CE1 HIS G 330 102.556 −142.937 147.467 1.00 125.67 ATOM 1429 NE2 HIS G 330 103.614 −143.617 147.061 1.00 125.50 ATOM 1430 N CYS G 331 103.519 −141.392 142.162 1.00 125.98 ATOM 1431 CA CYS G 331 103.471 −142.479 141.187 1.00 127.16 ATOM 1432 C CYS G 331 104.763 −143.292 141.212 1.00 129.17 ATOM 1433 O CYS G 331 105.756 −142.883 141.814 1.00 129.56 ATOM 1434 CB CYS G 331 103.263 −141.931 139.777 1.00 124.83 ATOM 1435 SG CYS G 331 101.784 −140.903 139.514 1.00 121.39 ATOM 1436 N ASN G 332 104.744 −144.441 140.542 1.00 131.21 ATOM 1437 CA ASN G 332 105.907 −145.317 140.491 1.00 133.03 ATOM 1438 C ASN G 332 106.019 −146.059 139.161 1.00 132.94 ATOM 1439 O ASN G 332 105.054 −146.665 138.696 1.00 133.74 ATOM 1440 CB ASN G 332 105.845 −146.346 141.625 1.00 135.06 ATOM 1441 CG ASN G 332 106.883 −146.090 142.699 1.00 138.61 ATOM 1442 OD1 ASN G 332 108.036 −145.797 142.379 1.00 140.34 ATOM 1443 ND2 ASN G 332 106.492 −146.199 143.969 1.00 141.14 ATOM 1444 N ILE G 333 107.205 −146.016 138.562 1.00 132.27 ATOM 1445 CA ILE G 333 107.458 −146.705 137.305 1.00 131.40 ATOM 1446 C ILE G 333 108.827 −147.371 137.344 1.00 131.17 ATOM 1447 O ILE G 333 109.685 −146.991 138.138 1.00 130.59 ATOM 1448 CB ILE G 333 107.438 −145.738 136.110 1.00 130.99 ATOM 1449 CG1 ILE G 333 108.336 −144.541 136.416 1.00 131.41 ATOM 1450 CG2 ILE G 333 106.013 −145.321 135.796 1.00 130.08 ATOM 1451 CD1 ILE G 333 108.808 −143.797 135.194 1.00 130.71 ATOM 1452 N SER G 334 109.027 −148.362 136.482 1.00 130.80 ATOM 1453 CA SER G 334 110.298 −149.071 136.417 1.00 130.47 ATOM 1454 C SER G 334 111.379 −148.202 135.781 1.00 129.18 ATOM 1455 O SER G 334 111.253 −147.785 134.630 1.00 128.30 ATOM 1456 CB SER G 334 110.137 −150.366 135.620 1.00 131.53 ATOM 1457 OG SER G 334 109.185 −151.224 136.226 1.00 134.33 ATOM 1458 N ARG G 335 112.441 −147.938 136.537 1.00 128.40 ATOM 1459 CA ARG G 335 113.550 −147.114 136.062 1.00 127.88 ATOM 1460 C ARG G 335 114.232 −147.713 134.831 1.00 127.39 ATOM 1461 O ARG G 335 114.594 −146.992 133.901 1.00 125.90 ATOM 1462 CB ARG G 335 114.588 −146.944 137.174 1.00 128.63 ATOM 1463 CG ARG G 335 115.721 −145.986 136.839 1.00 130.03 ATOM 1464 CD ARG G 335 115.354 −144.549 137.175 1.00 131.46 ATOM 1465 NE ARG G 335 116.464 −143.631 136.927 1.00 133.64 ATOM 1466 CZ ARG G 335 116.796 −143.164 135.728 1.00 135.08 ATOM 1467 NH1 ARG G 335 116.102 −143.521 134.655 1.00 135.62 ATOM 1468 NH2 ARG G 335 117.828 −142.340 135.600 1.00 136.66 ATOM 1469 N ALA G 336 114.409 −149.030 134.831 1.00 127.56 ATOM 1470 CA ALA G 336 115.060 −149.712 133.717 1.00 127.56 ATOM 1471 C ALA G 336 114.193 −149.726 132.462 1.00 127.53 ATOM 1472 O ALA G 336 114.702 −149.613 131.347 1.00 127.19 ATOM 1473 CB ALA G 336 115.419 −151.140 134.121 1.00 127.32 ATOM 1474 N LYS G 337 112.884 −149.870 132.653 1.00 127.34 ATOM 1475 CA LYS G 337 111.929 −149.897 131.547 1.00 126.12 ATOM 1476 C LYS G 337 111.697 −148.511 130.952 1.00 125.19 ATOM 1477 O LYS G 337 111.525 −148.370 129.742 1.00 125.25 ATOM 1478 CB LYS G 337 110.590 −150.483 132.019 1.00 125.26 ATOM 1479 CG LYS G 337 110.486 −152.006 131.948 1.00 125.56 ATOM 1480 CD LYS G 337 110.195 −152.482 130.524 1.00 125.22 ATOM 1481 CE LYS G 337 110.096 −154.003 130.442 1.00 125.33 ATOM 1482 NZ LYS G 337 109.878 −154.486 129.045 1.00 122.70 ATOM 1483 N TRP G 338 111.693 −147.488 131.802 1.00 123.88 ATOM 1484 CA TRP G 338 111.471 −146.120 131.343 1.00 122.35 ATOM 1485 C TRP G 338 112.656 −145.584 130.551 1.00 122.08 ATOM 1486 O TRP G 338 112.482 −144.934 129.521 1.00 121.22 ATOM 1487 CB TRP G 338 111.188 −145.199 132.535 1.00 121.06 ATOM 1488 CG TRP G 338 111.092 −143.744 132.172 1.00 119.31 ATOM 1489 CD1 TRP G 338 111.853 −142.726 132.669 1.00 119.14 ATOM 1490 CD2 TRP G 338 110.185 −143.145 131.235 1.00 118.77 ATOM 1491 NE1 TRP G 338 111.479 −141.531 132.103 1.00 119.01 ATOM 1492 CE2 TRP G 338 110.458 −141.758 131.220 1.00 118.35 ATOM 1493 CE3 TRP G 338 109.170 −143.644 130.409 1.00 118.58 ATOM 1494 CZ2 TRP G 338 109.751 −140.864 130.408 1.00 117.90 ATOM 1495 CZ3 TRP G 338 108.467 −142.753 129.601 1.00 118.02 ATOM 1496 CH2 TRP G 338 108.763 −141.378 129.609 1.00 117.53 ATOM 1497 N ASN G 339 113.860 −145.865 131.034 1.00 122.65 ATOM 1498 CA ASN G 339 115.068 −145.399 130.367 1.00 123.64 ATOM 1499 C ASN G 339 115.247 −146.081 129.015 1.00 122.72 ATOM 1500 O ASN G 339 115.779 −145.490 128.079 1.00 120.87 ATOM 1501 CB ASN G 339 116.292 −145.661 131.249 1.00 126.14 ATOM 1502 CG ASN G 339 117.430 −144.705 130.960 1.00 128.79 ATOM 1503 OD1 ASN G 339 117.338 −143.511 131.247 1.00 129.26 ATOM 1504 ND2 ASN G 339 118.508 −145.223 130.384 1.00 130.45 ATOM 1505 N ASP G 340 114.805 −147.331 128.922 1.00 122.55 ATOM 1506 CA ASP G 340 114.913 −148.080 127.676 1.00 122.48 ATOM 1507 C ASP G 340 113.925 −147.552 126.654 1.00 121.75 ATOM 1508 O ASP G 340 114.254 −147.398 125.482 1.00 121.24 ATOM 1509 CB ASP G 340 114.651 −149.569 127.913 1.00 123.36 ATOM 1510 CG ASP G 340 115.932 −150.373 128.021 1.00 124.46 ATOM 1511 OD1 ASP G 340 116.606 −150.547 126.987 1.00 124.57 ATOM 1512 OD2 ASP G 340 116.263 −150.820 129.138 1.00 124.24 ATOM 1513 N THR G 341 112.709 −147.277 127.107 1.00 121.23 ATOM 1514 CA THR G 341 111.678 −146.760 126.223 1.00 120.37 ATOM 1515 C THR G 341 112.005 −145.321 125.864 1.00 120.04 ATOM 1516 O THR G 341 111.571 −144.813 124.833 1.00 119.85 ATOM 1517 CB THR G 341 110.292 −146.798 126.885 1.00 119.50 ATOM 1518 OG1 THR G 341 110.387 −146.310 128.227 1.00 118.81 ATOM 1519 CG2 THR G 341 109.738 −148.202 126.892 1.00 119.32 ATOM 1520 N LEU G 342 112.780 −144.668 126.719 1.00 118.58 ATOM 1521 CA LEU G 342 113.172 −143.285 126.488 1.00 117.21 ATOM 1522 C LEU G 342 114.214 −143.283 125.372 1.00 117.06 ATOM 1523 O LEU G 342 114.277 −142.363 124.557 1.00 116.61 ATOM 1524 CB LEU G 342 113.757 −142.700 127.780 1.00 116.17 ATOM 1525 CG LEU G 342 113.453 −141.242 128.147 1.00 115.99 ATOM 1526 CD1 LEU G 342 113.803 −141.014 129.608 1.00 115.86 ATOM 1527 CD2 LEU G 342 114.230 −140.299 127.247 1.00 115.38 ATOM 1528 N LYS G 343 115.021 −144.340 125.341 1.00 117.43 ATOM 1529 CA LYS G 343 116.071 −144.497 124.340 1.00 117.14 ATOM 1530 C LYS G 343 115.481 −144.739 122.957 1.00 116.27 ATOM 1531 O LYS G 343 115.931 −144.159 121.970 1.00 114.89 ATOM 1532 CB LYS G 343 116.988 −145.668 124.720 1.00 118.24 ATOM 1533 CG LYS G 343 118.124 −145.916 123.741 1.00 119.11 ATOM 1534 CD LYS G 343 118.999 −147.081 124.184 1.00 118.05 ATOM 1535 CE LYS G 343 120.143 −147.321 123.205 1.00 117.07 ATOM 1536 NZ LYS G 343 121.015 −148.456 123.624 1.00 118.22 ATOM 1537 N GLN G 344 114.466 −145.594 122.890 1.00 115.18 ATOM 1538 CA GLN G 344 113.828 −145.899 121.617 1.00 114.37 ATOM 1539 C GLN G 344 113.146 −144.685 121.009 1.00 114.01 ATOM 1540 O GLN G 344 112.888 −144.642 119.807 1.00 113.70 ATOM 1541 CB GLN G 344 112.838 −147.051 121.780 1.00 113.68 ATOM 1542 CG GLN G 344 113.519 −148.414 121.728 1.00 114.75 ATOM 1543 CD GLN G 344 113.191 −149.300 122.912 1.00 115.83 ATOM 1544 OE1 GLN G 344 112.072 −149.795 123.044 1.00 116.37 ATOM 1545 NE2 GLN G 344 114.172 −149.505 123.784 1.00 116.57 ATOM 1546 N ILE G 345 112.858 −143.694 121.839 1.00 113.81 ATOM 1547 CA ILE G 345 112.241 −142.472 121.349 1.00 113.74 ATOM 1548 C ILE G 345 113.341 −141.701 120.641 1.00 114.51 ATOM 1549 O ILE G 345 113.143 −141.157 119.555 1.00 114.50 ATOM 1550 CB ILE G 345 111.689 −141.630 122.513 1.00 113.46 ATOM 1551 CG1 ILE G 345 110.481 −142.345 123.133 1.00 113.45 ATOM 1552 CG2 ILE G 345 111.291 −140.246 122.018 1.00 112.53 ATOM 1553 CD1 ILE G 345 109.980 −141.716 124.407 1.00 114.16 ATOM 1554 N VAL G 346 114.509 −141.680 121.271 1.00 115.23 ATOM 1555 CA VAL G 346 115.670 −140.996 120.729 1.00 116.13 ATOM 1556 C VAL G 346 116.128 −141.657 119.439 1.00 116.56 ATOM 1557 O VAL G 346 116.491 −140.980 118.476 1.00 115.69 ATOM 1558 CB VAL G 346 116.836 −141.021 121.727 1.00 116.71 ATOM 1559 CG1 VAL G 346 118.063 −140.394 121.104 1.00 116.76 ATOM 1560 CG2 VAL G 346 116.444 −140.284 122.999 1.00 117.56 ATOM 1561 N ILE G 347 116.105 −142.984 119.423 1.00 116.67 ATOM 1562 CA ILE G 347 116.513 −143.735 118.246 1.00 117.05 ATOM 1563 C ILE G 347 115.693 −143.356 117.022 1.00 117.43 ATOM 1564 O ILE G 347 116.235 −143.207 115.928 1.00 117.11 ATOM 1565 CB ILE G 347 116.366 −145.248 118.488 1.00 118.09 ATOM 1566 CG1 ILE G 347 117.391 −145.700 119.527 1.00 118.82 ATOM 1567 CG2 ILE G 347 116.546 −146.012 117.186 1.00 117.63 ATOM 1568 CD1 ILE G 347 118.828 −145.515 119.081 1.00 120.24 ATOM 1569 N LYS G 348 114.387 −143.199 117.215 1.00 118.10 ATOM 1570 CA LYS G 348 113.492 −142.836 116.125 1.00 119.28 ATOM 1571 C LYS G 348 113.477 −141.331 115.880 1.00 120.01 ATOM 1572 O LYS G 348 113.158 −140.883 114.780 1.00 119.90 ATOM 1573 CB LYS G 348 112.069 −143.326 116.416 1.00 119.85 ATOM 1574 CG LYS G 348 111.895 −144.844 116.394 1.00 120.97 ATOM 1575 CD LYS G 348 112.020 −145.410 114.980 1.00 122.36 ATOM 1576 CE LYS G 348 111.989 −146.937 114.982 1.00 123.02 ATOM 1577 NZ LYS G 348 112.225 −147.510 113.623 1.00 121.99 ATOM 1578 N LEU G 349 113.815 −140.550 116.903 1.00 120.97 ATOM 1579 CA LEU G 349 113.837 −139.098 116.757 1.00 122.27 ATOM 1580 C LEU G 349 115.045 −138.660 115.947 1.00 124.05 ATOM 1581 O LEU G 349 114.973 −137.710 115.170 1.00 124.00 ATOM 1582 CB LEU G 349 113.876 −138.406 118.122 1.00 121.94 ATOM 1583 CG LEU G 349 112.543 −138.095 118.810 1.00 122.12 ATOM 1584 CD1 LEU G 349 112.808 −137.386 120.131 1.00 122.10 ATOM 1585 CD2 LEU G 349 111.696 −137.209 117.900 1.00 122.34 ATOM 1586 N ARG G 350 116.161 −139.356 116.134 1.00 126.82 ATOM 1587 CA ARG G 350 117.382 −139.020 115.411 1.00 129.77 ATOM 1588 C ARG G 350 117.297 −139.583 114.004 1.00 130.79 ATOM 1589 O ARG G 350 118.100 −139.246 113.138 1.00 130.39 ATOM 1590 CB ARG G 350 118.618 −139.578 116.136 1.00 131.03 ATOM 1591 CG ARG G 350 118.728 −141.100 116.172 1.00 134.23 ATOM 1592 CD ARG G 350 119.545 −141.557 117.385 1.00 136.50 ATOM 1593 NE ARG G 350 120.947 −141.131 117.377 1.00 137.14 ATOM 1594 CZ ARG G 350 121.944 −141.836 116.849 1.00 137.25 ATOM 1595 NH1 ARG G 350 121.700 −143.008 116.276 1.00 136.86 ATOM 1596 NH2 ARG G 350 123.190 −141.381 116.914 1.00 136.51 ATOM 1597 N GLU G 351 116.307 −140.440 113.783 1.00 131.73 ATOM 1598 CA GLU G 351 116.108 −141.051 112.477 1.00 131.78 ATOM 1599 C GLU G 351 115.426 −140.024 111.574 1.00 131.64 ATOM 1600 O GLU G 351 115.425 −140.150 110.352 1.00 130.89 ATOM 1601 CB GLU G 351 115.250 −142.319 112.618 1.00 132.20 ATOM 1602 CG GLU G 351 115.735 −143.503 111.787 1.00 133.83 ATOM 1603 CD GLU G 351 114.933 −144.778 112.033 1.00 134.12 ATOM 1604 OE1 GLU G 351 114.970 −145.303 113.165 1.00 133.27 ATOM 1605 OE2 GLU G 351 114.267 −145.261 111.092 1.00 133.23 ATOM 1606 N GLN G 352 114.851 −138.998 112.197 1.00 131.55 ATOM 1607 CA GLN G 352 114.174 −137.930 111.469 1.00 131.20 ATOM 1608 C GLN G 352 115.029 −136.667 111.583 1.00 131.74 ATOM 1609 O GLN G 352 115.015 −135.810 110.703 1.00 131.22 ATOM 1610 CB GLN G 352 112.775 −137.684 112.055 1.00 129.40 ATOM 1611 CG GLN G 352 111.683 −137.483 111.010 1.00 128.29 ATOM 1612 CD GLN G 352 111.760 −136.141 110.302 1.00 128.13 ATOM 1613 OE1 GLN G 352 111.325 −136.007 109.158 1.00 128.02 ATOM 1614 NE2 GLN G 352 112.296 −135.137 110.986 1.00 127.02 ATOM 1615 N PHE G 353 115.781 −136.567 112.675 1.00 132.98 ATOM 1616 CA PHE G 353 116.654 −135.423 112.911 1.00 135.12 ATOM 1617 C PHE G 353 118.045 −135.862 113.357 1.00 136.10 ATOM 1618 O PHE G 353 118.362 −135.841 114.547 1.00 136.53 ATOM 1619 CB PHE G 353 116.054 −134.490 113.969 1.00 135.78 ATOM 1620 CG PHE G 353 114.963 −133.605 113.447 1.00 137.46 ATOM 1621 CD1 PHE G 353 113.645 −133.786 113.853 1.00 137.80 ATOM 1622 CD2 PHE G 353 115.255 −132.586 112.544 1.00 137.80 ATOM 1623 CE1 PHE G 353 112.631 −132.963 113.365 1.00 138.59 ATOM 1624 CE2 PHE G 353 114.249 −131.759 112.050 1.00 138.17 ATOM 1625 CZ PHE G 353 112.935 −131.948 112.461 1.00 138.87 ATOM 1626 N GLU G 354 118.871 −136.261 112.397 1.00 137.05 ATOM 1627 CA GLU G 354 120.224 −136.707 112.687 1.00 137.91 ATOM 1628 C GLU G 354 121.203 −135.540 112.616 1.00 137.70 ATOM 1629 O GLU G 354 120.881 −134.475 112.085 1.00 137.66 ATOM 1630 CB GLU G 354 120.615 −137.825 111.716 1.00 138.86 ATOM 1631 CG GLU G 354 121.921 −138.512 112.053 1.00 139.85 ATOM 1632 CD GLU G 354 122.022 −138.871 113.521 1.00 140.14 ATOM 1633 OE1 GLU G 354 121.152 −139.618 114.017 1.00 140.78 ATOM 1634 OE2 GLU G 354 122.976 −138.403 114.175 1.00 139.52 ATOM 1635 N ASN G 355 122.406 −135.754 113.142 1.00 137.40 ATOM 1636 CA ASN G 355 123.425 −134.703 113.192 1.00 136.85 ATOM 1637 C ASN G 355 122.937 −133.573 114.098 1.00 136.44 ATOM 1638 O ASN G 355 123.254 −132.412 113.913 1.00 137.04 ATOM 1639 CB ASN G 355 123.740 −134.195 111.776 1.00 136.54 ATOM 1640 CG ASN G 355 124.508 −135.220 110.949 1.00 135.79 ATOM 1641 OD1 ASN G 355 124.035 −136.328 110.725 1.00 135.13 ATOM 1642 ND2 ASN G 355 125.715 −134.853 110.514 1.00 135.21 ATOM 1643 N LYS G 357 122.152 −133.950 115.096 1.00 135.07 ATOM 1644 CA LYS G 357 121.606 −133.017 116.079 1.00 133.42 ATOM 1645 C LYS G 357 121.698 −133.716 117.421 1.00 131.94 ATOM 1646 O LYS G 357 121.977 −134.913 117.471 1.00 131.61 ATOM 1647 CB LYS G 357 120.137 −132.700 115.770 1.00 133.82 ATOM 1648 CG LYS G 357 119.862 −132.151 114.378 1.00 134.32 ATOM 1649 CD LYS G 357 119.821 −130.635 114.369 1.00 135.18 ATOM 1650 CE LYS G 357 119.478 −130.113 112.987 1.00 135.74 ATOM 1651 NZ LYS G 357 119.344 −128.636 112.997 1.00 135.57 ATOM 1652 N THR G 358 121.466 −132.974 118.499 1.00 130.25 ATOM 1653 CA THR G 358 121.499 −133.557 119.832 1.00 128.54 ATOM 1654 C THR G 358 120.142 −133.485 120.532 1.00 127.66 ATOM 1655 O THR G 358 119.636 −132.395 120.811 1.00 127.33 ATOM 1656 CB THR G 358 122.531 −132.868 120.749 1.00 127.87 ATOM 1657 OG1 THR G 358 123.852 −133.126 120.269 1.00 127.40 ATOM 1658 CG2 THR G 358 122.406 −133.397 122.167 1.00 127.41 ATOM 1659 N ILE G 359 119.558 −134.647 120.813 1.00 126.20 ATOM 1660 CA ILE G 359 118.258 −134.718 121.480 1.00 125.26 ATOM 1661 C ILE G 359 118.360 −134.591 123.005 1.00 124.58 ATOM 1662 O ILE G 359 118.904 −135.468 123.681 1.00 124.63 ATOM 1663 CB ILE G 359 117.528 −136.050 121.154 1.00 124.56 ATOM 1664 CG1 ILE G 359 117.243 −136.142 119.654 1.00 124.71 ATOM 1665 CG2 ILE G 359 116.212 −136.130 121.922 1.00 124.84 ATOM 1666 CD1 ILE G 359 118.474 −136.371 118.804 1.00 124.99 ATOM 1667 N VAL G 360 117.816 −133.503 123.541 1.00 123.68 ATOM 1668 CA VAL G 360 117.841 −133.248 124.977 1.00 122.86 ATOM 1669 C VAL G 360 116.417 −133.181 125.520 1.00 122.77 ATOM 1670 O VAL G 360 115.532 −132.627 124.874 1.00 122.31 ATOM 1671 CB VAL G 360 118.535 −131.907 125.278 1.00 122.10 ATOM 1672 CG1 VAL G 360 118.861 −131.806 126.759 1.00 121.81 ATOM 1673 CG2 VAL G 360 119.783 −131.772 124.427 1.00 122.35 ATOM 1674 N PHE G 361 116.201 −133.746 126.702 1.00 122.89 ATOM 1675 CA PHE G 361 114.881 −133.744 127.323 1.00 122.88 ATOM 1676 C PHE G 361 114.852 −132.840 128.544 1.00 123.80 ATOM 1677 O PHE G 361 115.619 −133.024 129.490 1.00 124.18 ATOM 1678 CB PHE G 361 114.486 −135.169 127.705 1.00 121.54 ATOM 1679 CG PHE G 361 114.075 −136.008 126.536 1.00 120.64 ATOM 1680 CD1 PHE G 361 112.802 −135.884 125.995 1.00 121.67 ATOM 1681 CD2 PHE G 361 114.967 −136.901 125.954 1.00 120.34 ATOM 1682 CE1 PHE G 361 112.419 −136.638 124.889 1.00 122.25 ATOM 1683 CE2 PHE G 361 114.596 −137.660 124.847 1.00 120.52 ATOM 1684 CZ PHE G 361 113.319 −137.528 124.314 1.00 121.45 ATOM 1685 N ASN G 362 113.954 −131.864 128.516 1.00 124.73 ATOM 1686 CA ASN G 362 113.837 −130.906 129.602 1.00 125.55 ATOM 1687 C ASN G 362 112.401 −130.831 130.118 1.00 124.88 ATOM 1688 O ASN G 362 111.485 −131.370 129.499 1.00 124.87 ATOM 1689 CB ASN G 362 114.294 −129.537 129.097 1.00 127.19 ATOM 1690 CG ASN G 362 114.691 −128.608 130.215 1.00 130.61 ATOM 1691 OD1 ASN G 362 113.874 −128.287 131.083 1.00 131.85 ATOM 1692 ND2 ASN G 362 115.948 −128.168 130.199 1.00 133.40 ATOM 1693 N HIS G 363 112.207 −130.159 131.248 1.00 124.22 ATOM 1694 CA HIS G 363 110.878 −130.014 131.826 1.00 123.37 ATOM 1695 C HIS G 363 110.003 −129.081 130.986 1.00 122.33 ATOM 1696 O HIS G 363 110.445 −128.552 129.965 1.00 123.35 ATOM 1697 CB HIS G 363 110.986 −129.485 133.261 1.00 123.55 ATOM 1698 CG HIS G 363 111.789 −128.228 133.388 1.00 123.69 ATOM 1699 ND1 HIS G 363 111.430 −127.051 132.769 1.00 123.31 ATOM 1700 CD2 HIS G 363 112.933 −127.966 134.063 1.00 124.89 ATOM 1701 CE1 HIS G 363 112.319 −126.118 133.056 1.00 123.86 ATOM 1702 NE2 HIS G 363 113.242 −126.646 133.839 1.00 125.14 ATOM 1703 N SER G 364 108.763 −128.876 131.419 1.00 119.87 ATOM 1704 CA SER G 364 107.853 −128.002 130.691 1.00 117.00 ATOM 1705 C SER G 364 108.279 −126.547 130.857 1.00 115.19 ATOM 1706 O SER G 364 108.577 −126.102 131.964 1.00 115.16 ATOM 1707 CB SER G 364 106.422 −128.192 131.192 1.00 116.69 ATOM 1708 OG SER G 364 105.495 −127.562 130.324 1.00 116.92 ATOM 1709 N SER G 365 108.307 −125.811 129.752 1.00 113.25 ATOM 1710 CA SER G 365 108.711 −124.411 129.770 1.00 112.58 ATOM 1711 C SER G 365 107.797 −123.480 130.566 1.00 112.63 ATOM 1712 O SER G 365 108.216 −122.389 130.949 1.00 113.24 ATOM 1713 CB SER G 365 108.848 −123.897 128.341 1.00 112.43 ATOM 1714 OG SER G 365 107.754 −124.318 127.550 1.00 112.84 ATOM 1715 N GLY G 366 106.559 −123.895 130.823 1.00 112.08 ATOM 1716 CA GLY G 366 105.661 −123.044 131.591 1.00 111.71 ATOM 1717 C GLY G 366 104.224 −123.031 131.111 1.00 111.01 ATOM 1718 O GLY G 366 103.920 −123.550 130.041 1.00 111.21 ATOM 1719 N GLY G 367 103.339 −122.439 131.908 1.00 110.29 ATOM 1720 CA GLY G 367 101.935 −122.374 131.538 1.00 109.86 ATOM 1721 C GLY G 367 101.013 −122.876 132.633 1.00 109.09 ATOM 1722 O GLY G 367 101.382 −122.880 133.806 1.00 110.03 ATOM 1723 N ASP G 368 99.810 −123.300 132.255 1.00 107.77 ATOM 1724 CA ASP G 368 98.847 −123.813 133.219 1.00 106.93 ATOM 1725 C ASP G 368 99.347 −125.117 133.825 1.00 105.42 ATOM 1726 O ASP G 368 99.888 −125.969 133.122 1.00 105.22 ATOM 1727 CB ASP G 368 97.490 −124.046 132.551 1.00 109.08 ATOM 1728 CG ASP G 368 96.754 −122.749 132.246 1.00 110.72 ATOM 1729 OD1 ASP G 368 96.346 −122.063 133.204 1.00 112.84 ATOM 1730 OD2 ASP G 368 96.587 −122.420 131.052 1.00 110.53 ATOM 1731 N PRO G 369 99.161 −125.290 135.143 1.00 104.21 ATOM 1732 CA PRO G 369 99.587 −126.484 135.874 1.00 103.74 ATOM 1733 C PRO G 369 99.165 −127.797 135.227 1.00 102.96 ATOM 1734 O PRO G 369 99.756 −128.842 135.495 1.00 103.69 ATOM 1735 CB PRO G 369 98.955 −126.279 137.243 1.00 104.51 ATOM 1736 CG PRO G 369 99.051 −124.796 137.406 1.00 104.97 ATOM 1737 CD PRO G 369 98.530 −124.330 136.063 1.00 104.21 ATOM 1738 N GLU G 370 98.148 −127.745 134.376 1.00 101.68 ATOM 1739 CA GLU G 370 97.676 −128.949 133.707 1.00 100.29 ATOM 1740 C GLU G 370 98.665 −129.450 132.663 1.00 99.24 ATOM 1741 O GLU G 370 98.741 −130.650 132.396 1.00 100.20 ATOM 1742 CB GLU G 370 96.316 −128.699 133.049 1.00 101.70 ATOM 1743 CG GLU G 370 95.129 −128.747 134.007 1.00 101.29 ATOM 1744 CD GLU G 370 94.927 −127.459 134.790 1.00 101.71 ATOM 1745 OE1 GLU G 370 94.058 −127.440 135.687 1.00 101.10 ATOM 1746 OE2 GLU G 370 95.628 −126.465 134.508 1.00 102.45 ATOM 1747 N ILE G 371 99.424 −128.532 132.077 1.00 97.76 ATOM 1748 CA ILE G 371 100.401 −128.891 131.058 1.00 96.84 ATOM 1749 C ILE G 371 101.755 −129.144 131.702 1.00 95.29 ATOM 1750 O ILE G 371 102.455 −130.104 131.369 1.00 94.66 ATOM 1751 CB ILE G 371 100.563 −127.756 130.041 1.00 96.73 ATOM 1752 CG1 ILE G 371 99.189 −127.193 129.678 1.00 96.23 ATOM 1753 CG2 ILE G 371 101.254 −128.276 128.792 1.00 98.30 ATOM 1754 CD1 ILE G 371 99.236 −125.769 129.192 1.00 96.31 ATOM 1755 N VAL G 372 102.111 −128.273 132.637 1.00 92.31 ATOM 1756 CA VAL G 372 103.376 −128.378 133.340 1.00 89.48 ATOM 1757 C VAL G 372 103.503 −129.702 134.081 1.00 87.73 ATOM 1758 O VAL G 372 104.586 −130.277 134.150 1.00 88.58 ATOM 1759 CB VAL G 372 103.533 −127.237 134.352 1.00 89.89 ATOM 1760 CG1 VAL G 372 104.936 −127.246 134.926 1.00 91.74 ATOM 1761 CG2 VAL G 372 103.233 −125.906 133.683 1.00 89.58 ATOM 1762 N MET G 373 102.395 −130.187 134.631 1.00 86.24 ATOM 1763 CA MET G 373 102.411 −131.444 135.364 1.00 86.32 ATOM 1764 C MET G 373 101.540 −132.498 134.689 1.00 86.85 ATOM 1765 O MET G 373 100.541 −132.174 134.051 1.00 86.82 ATOM 1766 CB MET G 373 101.930 −131.220 136.805 1.00 86.15 ATOM 1767 CG MET G 373 102.616 −130.059 137.512 1.00 85.92 ATOM 1768 SD MET G 373 103.120 −130.448 139.200 1.00 87.98 ATOM 1769 CE MET G 373 101.830 −129.658 140.161 1.00 88.57 ATOM 1770 N HIS G 374 101.930 −133.762 134.823 1.00 87.56 ATOM 1771 CA HIS G 374 101.161 −134.857 134.244 1.00 88.76 ATOM 1772 C HIS G 374 99.810 −134.931 134.944 1.00 90.65 ATOM 1773 O HIS G 374 99.699 −135.514 136.019 1.00 93.49 ATOM 1774 CB HIS G 374 101.905 −136.181 134.422 1.00 87.35 ATOM 1775 CG HIS G 374 101.079 −137.385 134.096 1.00 85.69 ATOM 1776 ND1 HIS G 374 100.563 −137.614 132.839 1.00 85.77 ATOM 1777 CD2 HIS G 374 100.677 −138.425 134.863 1.00 85.18 ATOM 1778 CE1 HIS G 374 99.881 −138.745 132.845 1.00 87.31 ATOM 1779 NE2 HIS G 374 99.934 −139.257 134.061 1.00 86.65 ATOM 1780 N SER G 375 98.788 −134.346 134.330 1.00 91.35 ATOM 1781 CA SER G 375 97.454 −134.327 134.918 1.00 91.01 ATOM 1782 C SER G 375 96.531 −135.438 134.431 1.00 90.01 ATOM 1783 O SER G 375 96.426 −135.685 133.233 1.00 90.38 ATOM 1784 CB SER G 375 96.796 −132.978 134.636 1.00 93.11 ATOM 1785 OG SER G 375 96.788 −132.708 133.244 1.00 93.88 ATOM 1786 N PHE G 376 95.860 −136.101 135.368 1.00 90.06 ATOM 1787 CA PHE G 376 94.920 −137.166 135.037 1.00 93.27 ATOM 1788 C PHE G 376 93.895 −137.317 136.156 1.00 95.94 ATOM 1789 O PHE G 376 94.034 −136.702 137.212 1.00 95.54 ATOM 1790 CB PHE G 376 95.649 −138.495 134.805 1.00 92.86 ATOM 1791 CG PHE G 376 96.283 −139.076 136.037 1.00 93.02 ATOM 1792 CD1 PHE G 376 97.542 −138.660 136.454 1.00 93.40 ATOM 1793 CD2 PHE G 376 95.628 −140.065 136.766 1.00 92.09 ATOM 1794 CE1 PHE G 376 98.144 −139.223 137.581 1.00 93.87 ATOM 1795 CE2 PHE G 376 96.218 −140.634 137.892 1.00 92.28 ATOM 1796 CZ PHE G 376 97.479 −140.214 138.300 1.00 94.05 ATOM 1797 N ASN G 377 92.870 −138.132 135.930 1.00 99.59 ATOM 1798 CA ASN G 377 91.825 −138.327 136.931 1.00 104.81 ATOM 1799 C ASN G 377 91.355 −139.774 137.059 1.00 107.26 ATOM 1800 O ASN G 377 91.034 −140.429 136.068 1.00 107.33 ATOM 1801 CB ASN G 377 90.625 −137.442 136.598 1.00 107.57 ATOM 1802 CG ASN G 377 90.145 −137.635 135.176 1.00 110.35 ATOM 1803 OD1 ASN G 377 90.827 −137.256 134.223 1.00 112.46 ATOM 1804 ND2 ASN G 377 88.974 −138.242 135.023 1.00 111.65 ATOM 1805 N CYS G 378 91.313 −140.259 138.296 1.00 110.71 ATOM 1806 CA CYS G 378 90.878 −141.621 138.595 1.00 113.87 ATOM 1807 C CYS G 378 90.247 −141.634 139.988 1.00 114.07 ATOM 1808 O CYS G 378 90.894 −141.266 140.966 1.00 113.69 ATOM 1809 CB CYS G 378 92.069 −142.601 138.540 1.00 116.89 ATOM 1810 SG CYS G 378 93.430 −142.309 139.720 1.00 121.15 ATOM 1811 N GLY G 379 88.985 −142.047 140.080 1.00 113.75 ATOM 1812 CA GLY G 379 88.320 −142.076 141.373 1.00 112.55 ATOM 1813 C GLY G 379 87.547 −140.800 141.651 1.00 111.47 ATOM 1814 O GLY G 379 86.731 −140.736 142.570 1.00 112.00 ATOM 1815 N GLY G 380 87.809 −139.776 140.849 1.00 109.49 ATOM 1816 CA GLY G 380 87.123 −138.513 141.024 1.00 107.11 ATOM 1817 C GLY G 380 88.074 −137.401 141.410 1.00 105.53 ATOM 1818 O GLY G 380 87.672 −136.246 141.521 1.00 106.59 ATOM 1819 N GLU G 381 89.342 −137.743 141.611 1.00 102.89 ATOM 1820 CA GLU G 381 90.339 −136.749 141.989 1.00 100.20 ATOM 1821 C GLU G 381 91.269 −136.414 140.832 1.00 97.39 ATOM 1822 O GLU G 381 91.658 −137.291 140.062 1.00 97.65 ATOM 1823 CB GLU G 381 91.165 −137.252 143.174 1.00 101.99 ATOM 1824 CG GLU G 381 90.341 −137.669 144.376 1.00 104.32 ATOM 1825 CD GLU G 381 89.409 −136.574 144.853 1.00 106.86 ATOM 1826 OE1 GLU G 381 89.884 −135.439 145.071 1.00 108.66 ATOM 1827 OE2 GLU G 381 88.201 −136.853 145.014 1.00 108.04 ATOM 1828 N PHE G 382 91.629 −135.140 140.719 1.00 93.73 ATOM 1829 CA PHE G 382 92.513 −134.697 139.648 1.00 89.57 ATOM 1830 C PHE G 382 93.963 −134.629 140.104 1.00 88.33 ATOM 1831 O PHE G 382 94.338 −133.753 140.882 1.00 88.16 ATOM 1832 CB PHE G 382 92.073 −133.326 139.134 1.00 86.63 ATOM 1833 CG PHE G 382 90.700 −133.321 138.523 1.00 84.43 ATOM 1834 CD1 PHE G 382 89.570 −133.512 139.313 1.00 82.70 ATOM 1835 CD2 PHE G 382 90.536 −133.130 137.155 1.00 83.85 ATOM 1836 CE1 PHE G 382 88.298 −133.513 138.749 1.00 80.29 ATOM 1837 CE2 PHE G 382 89.268 −133.130 136.584 1.00 82.03 ATOM 1838 CZ PHE G 382 88.149 −133.321 137.383 1.00 80.22 ATOM 1839 N PHE G 383 94.777 −135.555 139.607 1.00 87.21 ATOM 1840 CA PHE G 383 96.190 −135.607 139.965 1.00 86.08 ATOM 1841 C PHE G 383 97.049 −134.663 139.136 1.00 85.60 ATOM 1842 O PHE G 383 96.735 −134.368 137.984 1.00 85.11 ATOM 1843 CB PHE G 383 96.727 −137.032 139.805 1.00 85.28 ATOM 1844 CG PHE G 383 96.120 −138.022 140.755 1.00 85.57 ATOM 1845 CD1 PHE G 383 94.790 −138.408 140.627 1.00 85.90 ATOM 1846 CD2 PHE G 383 96.880 −138.571 141.782 1.00 85.81 ATOM 1847 CE1 PHE G 383 94.226 −139.327 141.508 1.00 85.70 ATOM 1848 CE2 PHE G 383 96.326 −139.489 142.667 1.00 85.26 ATOM 1849 CZ PHE G 383 94.997 −139.868 142.530 1.00 84.70 ATOM 1850 N TYR G 384 98.135 −134.190 139.736 1.00 85.21 ATOM 1851 CA TYR G 384 99.071 −133.295 139.061 1.00 86.70 ATOM 1852 C TYR G 384 100.504 −133.685 139.415 1.00 89.54 ATOM 1853 O TYR G 384 101.132 −133.047 140.255 1.00 90.93 ATOM 1854 CB TYR G 384 98.812 −131.845 139.473 1.00 85.32 ATOM 1855 CG TYR G 384 97.548 −131.256 138.895 1.00 83.12 ATOM 1856 CD1 TYR G 384 96.321 −131.416 139.533 1.00 82.42 ATOM 1857 CD2 TYR G 384 97.579 −130.555 137.690 1.00 81.60 ATOM 1858 CE1 TYR G 384 95.153 −130.891 138.983 1.00 82.41 ATOM 1859 CE2 TYR G 384 96.422 −130.029 137.132 1.00 81.05 ATOM 1860 CZ TYR G 384 95.214 −130.200 137.782 1.00 81.32 ATOM 1861 OH TYR G 384 94.070 −129.681 137.223 1.00 78.86 ATOM 1862 N CYS G 385 101.010 −134.733 138.764 1.00 93.00 ATOM 1863 CA CYS G 385 102.358 −135.249 139.016 1.00 96.10 ATOM 1864 C CYS G 385 103.432 −134.478 138.255 1.00 98.98 ATOM 1865 O CYS G 385 103.284 −134.196 137.064 1.00 100.31 ATOM 1866 CB CYS G 385 102.448 −136.727 138.625 1.00 96.17 ATOM 1867 SG CYS G 385 101.237 −137.831 139.415 1.00 97.03 ATOM 1868 N ASN G 386 104.522 −134.158 138.944 1.00 101.88 ATOM 1869 CA ASN G 386 105.630 −133.416 138.351 1.00 105.68 ATOM 1870 C ASN G 386 106.483 −134.318 137.460 1.00 109.06 ATOM 1871 O ASN G 386 107.126 −135.249 137.940 1.00 110.00 ATOM 1872 CB ASN G 386 106.488 −132.802 139.464 1.00 104.65 ATOM 1873 CG ASN G 386 107.278 −131.592 138.997 1.00 104.49 ATOM 1874 OD1 ASN G 386 107.793 −130.826 139.811 1.00 105.86 ATOM 1875 ND2 ASN G 386 107.380 −131.417 137.682 1.00 103.57 ATOM 1876 N SER G 387 106.489 −134.033 136.161 1.00 112.28 ATOM 1877 CA SER G 387 107.255 −134.828 135.204 1.00 115.20 ATOM 1878 C SER G 387 108.613 −134.207 134.897 1.00 117.38 ATOM 1879 O SER G 387 109.080 −134.244 133.756 1.00 118.83 ATOM 1880 CB SER G 387 106.468 −134.982 133.901 1.00 114.78 ATOM 1881 OG SER G 387 106.259 −133.722 133.290 1.00 115.93 ATOM 1882 N ALA G 388 109.242 −133.635 135.916 1.00 118.94 ATOM 1883 CA ALA G 388 110.543 −133.004 135.747 1.00 120.08 ATOM 1884 C ALA G 388 111.650 −134.046 135.640 1.00 120.63 ATOM 1885 O ALA G 388 112.518 −133.955 134.776 1.00 121.23 ATOM 1886 CB ALA G 388 110.821 −132.064 136.915 1.00 120.48 ATOM 1887 N GLN G 389 111.612 −135.038 136.523 1.00 121.07 ATOM 1888 CA GLN G 389 112.616 −136.094 136.531 1.00 121.87 ATOM 1889 C GLN G 389 112.436 −137.082 135.383 1.00 121.47 ATOM 1890 O GLN G 389 113.415 −137.619 134.864 1.00 122.53 ATOM 1891 CB GLN G 389 112.584 −136.833 137.870 1.00 123.58 ATOM 1892 CG GLN G 389 111.184 −137.051 138.405 1.00 127.91 ATOM 1893 CD GLN G 389 111.168 −137.823 139.708 1.00 130.19 ATOM 1894 OE1 GLN G 389 111.948 −137.547 140.620 1.00 132.91 ATOM 1895 NE2 GLN G 389 110.266 −138.791 139.806 1.00 131.56 ATOM 1896 N LEU G 390 111.189 −137.319 134.987 1.00 120.77 ATOM 1897 CA LEU G 390 110.899 −138.241 133.892 1.00 119.93 ATOM 1898 C LEU G 390 111.556 −137.810 132.589 1.00 119.16 ATOM 1899 O LEU G 390 112.076 −138.639 131.843 1.00 119.29 ATOM 1900 CB LEU G 390 109.392 −138.349 133.667 1.00 120.27 ATOM 1901 CG LEU G 390 108.609 −139.237 134.633 1.00 120.93 ATOM 1902 CD1 LEU G 390 107.122 −139.075 134.385 1.00 122.76 ATOM 1903 CD2 LEU G 390 109.028 −140.682 134.437 1.00 121.13 ATOM 1904 N PHE G 391 111.525 −136.512 132.312 1.00 117.95 ATOM 1905 CA PHE G 391 112.116 −135.993 131.088 1.00 116.69 ATOM 1906 C PHE G 391 113.329 −135.117 131.375 1.00 116.29 ATOM 1907 O PHE G 391 113.311 −133.915 131.123 1.00 116.61 ATOM 1908 CB PHE G 391 111.076 −135.193 130.296 1.00 115.47 ATOM 1909 CG PHE G 391 109.902 −136.012 129.830 1.00 113.79 ATOM 1910 CD1 PHE G 391 108.889 −136.372 130.713 1.00 112.00 ATOM 1911 CD2 PHE G 391 109.814 −136.430 128.504 1.00 113.65 ATOM 1912 CE1 PHE G 391 107.806 −137.138 130.284 1.00 111.30 ATOM 1913 CE2 PHE G 391 108.735 −137.197 128.066 1.00 112.65 ATOM 1914 CZ PHE G 391 107.730 −137.550 128.959 1.00 111.37 ATOM 1915 N ASN G 392 114.386 −135.730 131.900 1.00 116.37 ATOM 1916 CA ASN G 392 115.614 −135.010 132.219 1.00 116.90 ATOM 1917 C ASN G 392 116.832 −135.861 131.881 1.00 117.22 ATOM 1918 O ASN G 392 117.371 −136.552 132.746 1.00 117.20 ATOM 1919 CB ASN G 392 115.653 −134.660 133.710 1.00 117.23 ATOM 1920 CG ASN G 392 116.788 −133.711 134.059 1.00 117.04 ATOM 1921 OD1 ASN G 392 117.373 −133.793 135.141 1.00 116.31 ATOM 1922 ND2 ASN G 392 117.091 −132.792 133.148 1.00 115.97 ATOM 1923 N SER G 393 117.264 −135.811 130.628 1.00 117.25 ATOM 1924 CA SER G 393 118.420 −136.587 130.199 1.00 117.84 ATOM 1925 C SER G 393 118.898 −136.099 128.838 1.00 118.76 ATOM 1926 O SER G 393 118.091 −135.750 127.979 1.00 118.46 ATOM 1927 CB SER G 393 118.059 −138.076 130.130 1.00 117.40 ATOM 1928 OG SER G 393 116.915 −138.287 129.323 1.00 117.90 ATOM 1929 N THR G 394 120.213 −136.069 128.648 1.00 120.79 ATOM 1930 CA THR G 394 120.788 −135.615 127.390 1.00 122.12 ATOM 1931 C THR G 394 121.239 −136.811 126.565 1.00 123.64 ATOM 1932 O THR G 394 121.846 −137.738 127.096 1.00 123.04 ATOM 1933 CB THR G 394 122.003 −134.711 127.640 1.00 121.38 ATOM 1934 OG1 THR G 394 121.701 −133.792 128.694 1.00 121.49 ATOM 1935 CG2 THR G 394 122.347 −133.924 126.390 1.00 120.33 ATOM 1936 N TRP G 395 120.938 −136.791 125.271 1.00 125.53 ATOM 1937 CA TRP G 395 121.324 −137.885 124.389 1.00 127.71 ATOM 1938 C TRP G 395 122.040 −137.385 123.138 1.00 130.76 ATOM 1939 O TRP G 395 121.444 −136.713 122.296 1.00 130.73 ATOM 1940 CB TRP G 395 120.092 −138.696 123.976 1.00 124.98 ATOM 1941 CG TRP G 395 119.330 −139.263 125.127 1.00 122.80 ATOM 1942 CD1 TRP G 395 118.578 −138.573 126.032 1.00 122.44 ATOM 1943 CD2 TRP G 395 119.259 −140.641 125.511 1.00 121.88 ATOM 1944 NE1 TRP G 395 118.041 −139.435 126.957 1.00 122.03 ATOM 1945 CE2 TRP G 395 118.442 −140.710 126.662 1.00 121.61 ATOM 1946 CE3 TRP G 395 119.804 −141.823 124.995 1.00 122.03 ATOM 1947 CZ2 TRP G 395 118.159 −141.918 127.308 1.00 121.03 ATOM 1948 CZ3 TRP G 395 119.521 −143.024 125.638 1.00 121.12 ATOM 1949 CH2 TRP G 395 118.705 −143.061 126.782 1.00 120.35 ATOM 1950 N ASN G 396 123.322 −137.722 123.023 1.00 134.68 ATOM 1951 CA ASN G 396 124.132 −137.319 121.877 1.00 138.49 ATOM 1952 C ASN G 396 125.278 −138.306 121.699 1.00 140.34 ATOM 1953 O ASN G 396 126.028 −138.237 120.723 1.00 140.16 ATOM 1954 CB ASN G 396 124.702 −135.914 122.091 1.00 139.54 ATOM 1955 CG ASN G 396 125.710 −135.858 123.225 1.00 140.48 ATOM 1956 OD1 ASN G 396 125.396 −136.194 124.367 1.00 140.41 ATOM 1957 ND2 ASN G 396 126.929 −135.431 122.914 1.00 139.91 ATOM 1958 N ASN G 397 125.405 −139.223 122.653 1.00 142.71 ATOM 1959 CA ASN G 397 126.461 −140.225 122.616 1.00 145.52 ATOM 1960 C ASN G 397 126.235 −141.263 123.712 1.00 147.30 ATOM 1961 O ASN G 397 126.975 −141.314 124.696 1.00 147.83 ATOM 1962 CB ASN G 397 127.820 −139.546 122.804 1.00 145.45 ATOM 1963 CG ASN G 397 128.980 −140.452 122.449 1.00 146.09 ATOM 1964 OD1 ASN G 397 130.135 −140.031 122.478 1.00 147.69 ATOM 1965 ND2 ASN G 397 128.680 −141.700 122.109 1.00 146.44 ATOM 1966 N ASN G 401 125.206 −142.087 123.536 1.00 148.95 ATOM 1967 CA ASN G 401 124.874 −143.125 124.505 1.00 150.19 ATOM 1968 C ASN G 401 124.087 −144.258 123.850 1.00 151.32 ATOM 1969 O ASN G 401 122.864 −144.187 123.729 1.00 151.15 ATOM 1970 CB ASN G 401 124.057 −142.526 125.654 1.00 149.72 ATOM 1971 CG ASN G 401 123.716 −143.547 126.723 1.00 150.07 ATOM 1972 OD1 ASN G 401 123.043 −144.543 126.455 1.00 150.13 ATOM 1973 ND2 ASN G 401 124.180 −143.304 127.943 1.00 150.04 ATOM 1974 N THR G 402 124.798 −145.301 123.431 1.00 152.32 ATOM 1975 CA THR G 402 124.171 −146.452 122.790 1.00 152.72 ATOM 1976 C THR G 402 124.884 −147.746 123.178 1.00 152.78 ATOM 1977 O THR G 402 125.762 −148.222 122.457 1.00 152.62 ATOM 1978 CB THR G 402 124.193 −146.315 121.249 1.00 152.55 ATOM 1979 OG1 THR G 402 123.528 −145.105 120.864 1.00 152.61 ATOM 1980 CG2 THR G 402 123.489 −147.498 120.597 1.00 152.80 ATOM 1981 N GLU G 403 124.503 −148.307 124.322 1.00 153.02 ATOM 1982 CA GLU G 403 125.102 −149.547 124.806 1.00 153.40 ATOM 1983 C GLU G 403 124.013 −150.508 125.281 1.00 153.32 ATOM 1984 O GLU G 403 123.311 −151.112 124.468 1.00 152.98 ATOM 1985 CB GLU G 403 126.074 −149.251 125.952 1.00 153.38 ATOM 1986 CG GLU G 403 126.971 −150.422 126.323 1.00 154.46 ATOM 1987 CD GLU G 403 127.851 −150.127 127.522 1.00 155.23 ATOM 1988 OE1 GLU G 403 128.568 −149.104 127.499 1.00 155.71 ATOM 1989 OE2 GLU G 403 127.828 −150.921 128.486 1.00 155.97 ATOM 1990 N GLY G 404 123.875 −150.647 126.597 1.00 153.51 ATOM 1991 CA GLY G 404 122.862 −151.531 127.148 1.00 153.40 ATOM 1992 C GLY G 404 123.409 −152.822 127.728 1.00 153.73 ATOM 1993 O GLY G 404 123.831 −153.715 126.991 1.00 153.69 ATOM 1994 N SER G 405 123.400 −152.922 129.054 1.00 153.35 ATOM 1995 CA SER G 405 123.888 −154.112 129.745 1.00 152.70 ATOM 1996 C SER G 405 123.183 −154.291 131.086 1.00 152.14 ATOM 1997 O SER G 405 122.394 −155.221 131.259 1.00 151.89 ATOM 1998 CB SER G 405 125.401 −154.021 129.962 1.00 152.88 ATOM 1999 OG SER G 405 126.096 −154.051 128.728 1.00 152.70 ATOM 2000 N ASN G 406 123.473 −153.398 132.031 1.00 151.38 ATOM 2001 CA ASN G 406 122.864 −153.445 133.359 1.00 150.36 ATOM 2002 C ASN G 406 123.489 −152.410 134.294 1.00 149.65 ATOM 2003 O ASN G 406 124.666 −152.503 134.641 1.00 149.18 ATOM 2004 CB ASN G 406 123.020 −154.842 133.970 1.00 150.31 ATOM 2005 CG ASN G 406 122.212 −155.018 135.243 1.00 150.00 ATOM 2006 OD1 ASN G 406 122.418 −154.308 136.227 1.00 150.04 ATOM 2007 ND2 ASN G 406 121.284 −155.970 135.228 1.00 148.55 ATOM 2008 N ASN G 407 122.691 −151.425 134.696 1.00 149.20 ATOM 2009 CA ASN G 407 123.153 −150.371 135.596 1.00 148.98 ATOM 2010 C ASN G 407 122.039 −149.959 136.557 1.00 148.75 ATOM 2011 O ASN G 407 120.905 −149.720 136.141 1.00 148.64 ATOM 2012 CB ASN G 407 123.622 −149.154 134.792 1.00 148.85 ATOM 2013 CG ASN G 407 124.837 −149.454 133.934 1.00 148.15 ATOM 2014 OD1 ASN G 407 125.883 −149.861 134.440 1.00 147.21 ATOM 2015 ND2 ASN G 407 124.704 −149.252 132.627 1.00 146.76 ATOM 2016 N THR G 408 122.372 −149.876 137.843 1.00 148.42 ATOM 2017 CA THR G 408 121.400 −149.505 138.866 1.00 147.81 ATOM 2018 C THR G 408 121.620 −148.095 139.413 1.00 147.62 ATOM 2019 O THR G 408 122.740 −147.710 139.750 1.00 147.36 ATOM 2020 CB THR G 408 121.433 −150.503 140.047 1.00 147.47 ATOM 2021 OG1 THR G 408 121.128 −151.820 139.570 1.00 146.97 ATOM 2022 CG2 THR G 408 120.415 −150.110 141.110 1.00 147.04 ATOM 2023 N GLU G 409 120.532 −147.333 139.497 1.00 147.14 ATOM 2024 CA GLU G 409 120.563 −145.965 140.005 1.00 146.36 ATOM 2025 C GLU G 409 119.161 −145.527 140.417 1.00 145.32 ATOM 2026 O GLU G 409 118.354 −145.122 139.579 1.00 145.40 ATOM 2027 CB GLU G 409 121.116 −145.012 138.938 1.00 146.73 ATOM 2028 CG GLU G 409 120.856 −143.531 139.211 1.00 147.62 ATOM 2029 CD GLU G 409 121.396 −143.060 140.552 1.00 148.32 ATOM 2030 OE1 GLU G 409 121.186 −141.875 140.891 1.00 147.74 ATOM 2031 OE2 GLU G 409 122.029 −143.866 141.267 1.00 149.23 ATOM 2032 N GLY G 410 118.878 −145.613 141.713 1.00 143.74 ATOM 2033 CA GLY G 410 117.570 −145.228 142.210 1.00 141.66 ATOM 2034 C GLY G 410 116.524 −146.283 141.903 1.00 140.56 ATOM 2035 O GLY G 410 115.851 −146.210 140.874 1.00 140.48 ATOM 2036 N ASN G 412 116.401 −147.261 142.799 1.00 138.86 ATOM 2037 CA ASN G 412 115.446 −148.363 142.670 1.00 136.44 ATOM 2038 C ASN G 412 114.351 −148.049 141.651 1.00 134.58 ATOM 2039 O ASN G 412 114.474 −148.377 140.470 1.00 133.27 ATOM 2040 CB ASN G 412 114.818 −148.658 144.038 1.00 137.07 ATOM 2041 CG ASN G 412 114.127 −150.009 144.090 1.00 138.01 ATOM 2042 OD1 ASN G 412 113.251 −150.306 143.279 1.00 138.79 ATOM 2043 ND2 ASN G 412 114.519 −150.835 145.055 1.00 137.47 ATOM 2044 N THR G 413 113.283 −147.412 142.121 1.00 132.39 ATOM 2045 CA THR G 413 112.167 −147.028 141.264 1.00 129.59 ATOM 2046 C THR G 413 111.876 −145.553 141.502 1.00 127.51 ATOM 2047 O THR G 413 111.733 −145.116 142.645 1.00 127.21 ATOM 2048 CB THR G 413 110.899 −147.848 141.575 1.00 129.45 ATOM 2049 OG1 THR G 413 110.560 −147.703 142.959 1.00 130.30 ATOM 2050 CG2 THR G 413 111.125 −149.319 141.259 1.00 129.33 ATOM 2051 N ILE G 414 111.792 −144.788 140.418 1.00 125.10 ATOM 2052 CA ILE G 414 111.543 −143.356 140.515 1.00 122.12 ATOM 2053 C ILE G 414 110.120 −143.022 140.958 1.00 119.27 ATOM 2054 O ILE G 414 109.151 −143.618 140.489 1.00 118.60 ATOM 2055 CB ILE G 414 111.838 −142.653 139.169 1.00 121.95 ATOM 2056 CG1 ILE G 414 111.801 −141.138 139.358 1.00 122.52 ATOM 2057 CG2 ILE G 414 110.830 −143.086 138.118 1.00 121.32 ATOM 2058 CD1 ILE G 414 112.797 −140.620 140.384 1.00 122.64 ATOM 2059 N THR G 415 110.003 −142.060 141.866 1.00 115.70 ATOM 2060 CA THR G 415 108.704 −141.642 142.387 1.00 111.52 ATOM 2061 C THR G 415 108.362 −140.206 141.981 1.00 109.61 ATOM 2062 O THR G 415 109.175 −139.293 142.141 1.00 109.81 ATOM 2063 CB THR G 415 108.676 −141.739 143.923 1.00 110.78 ATOM 2064 OG1 THR G 415 109.874 −141.165 144.460 1.00 110.36 ATOM 2065 CG2 THR G 415 108.569 −143.179 144.369 1.00 109.69 ATOM 2066 N LEU G 416 107.150 −140.018 141.463 1.00 106.18 ATOM 2067 CA LEU G 416 106.684 −138.706 141.012 1.00 103.07 ATOM 2068 C LEU G 416 105.914 −137.919 142.070 1.00 101.81 ATOM 2069 O LEU G 416 104.998 −138.443 142.708 1.00 101.50 ATOM 2070 CB LEU G 416 105.775 −138.847 139.791 1.00 101.73 ATOM 2071 CG LEU G 416 106.344 −139.279 138.433 1.00 101.54 ATOM 2072 CD1 LEU G 416 107.506 −138.367 138.062 1.00 100.93 ATOM 2073 CD2 LEU G 416 106.797 −140.724 138.497 1.00 102.75 ATOM 2074 N PRO G 417 106.269 −136.638 142.261 1.00 100.49 ATOM 2075 CA PRO G 417 105.601 −135.778 143.242 1.00 99.11 ATOM 2076 C PRO G 417 104.244 −135.385 142.674 1.00 97.27 ATOM 2077 O PRO G 417 104.181 −134.634 141.706 1.00 96.57 ATOM 2078 CB PRO G 417 106.539 −134.573 143.338 1.00 99.33 ATOM 2079 CG PRO G 417 107.875 −135.120 142.895 1.00 100.96 ATOM 2080 CD PRO G 417 107.462 −135.964 141.726 1.00 101.14 ATOM 2081 N CYS G 418 103.158 −135.878 143.255 1.00 96.07 ATOM 2082 CA CYS G 418 101.840 −135.543 142.722 1.00 95.36 ATOM 2083 C CYS G 418 100.974 −134.814 143.737 1.00 94.31 ATOM 2084 O CYS G 418 101.186 −134.933 144.941 1.00 93.95 ATOM 2085 CB CYS G 418 101.124 −136.816 142.273 1.00 96.19 ATOM 2086 SG CYS G 418 100.205 −136.655 140.711 1.00 99.96 ATOM 2087 N ARG G 419 99.992 −134.065 143.243 1.00 93.30 ATOM 2088 CA ARG G 419 99.085 −133.325 144.112 1.00 92.31 ATOM 2089 C ARG G 419 97.658 −133.284 143.571 1.00 90.72 ATOM 2090 O ARG G 419 97.433 −132.982 142.396 1.00 90.53 ATOM 2091 CB ARG G 419 99.596 −131.890 144.314 1.00 93.73 ATOM 2092 CG ARG G 419 98.698 −131.006 145.181 1.00 95.93 ATOM 2093 CD ARG G 419 99.220 −129.571 145.236 1.00 99.25 ATOM 2094 NE ARG G 419 98.204 −128.611 145.670 1.00 100.53 ATOM 2095 CZ ARG G 419 97.837 −128.412 146.933 1.00 100.92 ATOM 2096 NH1 ARG G 419 98.402 −129.102 147.916 1.00 100.24 ATOM 2097 NH2 ARG G 419 96.900 −127.517 147.214 1.00 100.94 ATOM 2098 N ILE G 420 96.699 −133.601 144.436 1.00 88.67 ATOM 2099 CA ILE G 420 95.283 −133.579 144.078 1.00 86.76 ATOM 2100 C ILE G 420 94.765 −132.157 144.276 1.00 86.13 ATOM 2101 O ILE G 420 95.033 −131.530 145.302 1.00 86.62 ATOM 2102 CB ILE G 420 94.463 −134.540 144.969 1.00 85.30 ATOM 2103 CG1 ILE G 420 94.795 −135.997 144.627 1.00 84.63 ATOM 2104 CG2 ILE G 420 92.977 −134.295 144.768 1.00 85.53 ATOM 2105 CD1 ILE G 420 96.188 −136.429 145.018 1.00 84.54 ATOM 2106 N LYS G 421 94.021 −131.645 143.302 1.00 84.49 ATOM 2107 CA LYS G 421 93.523 −130.279 143.400 1.00 83.10 ATOM 2108 C LYS G 421 92.006 −130.151 143.259 1.00 83.34 ATOM 2109 O LYS G 421 91.341 −131.023 142.702 1.00 83.53 ATOM 2110 CB LYS G 421 94.224 −129.405 142.343 1.00 82.25 ATOM 2111 CG LYS G 421 95.756 −129.478 142.395 1.00 82.29 ATOM 2112 CD LYS G 421 96.428 −128.598 141.347 1.00 81.95 ATOM 2113 CE LYS G 421 97.882 −128.375 141.743 1.00 84.09 ATOM 2114 NZ LYS G 421 98.489 −127.187 141.078 1.00 83.94 ATOM 2115 N GLN G 422 91.471 −129.045 143.768 1.00 83.63 ATOM 2116 CA GLN G 422 90.040 −128.764 143.702 1.00 82.61 ATOM 2117 C GLN G 422 89.728 −127.802 142.565 1.00 80.65 ATOM 2118 O GLN G 422 88.823 −128.044 141.770 1.00 78.92 ATOM 2119 CB GLN G 422 89.553 −128.181 145.033 1.00 84.13 ATOM 2120 CG GLN G 422 89.286 −129.228 146.109 1.00 88.24 ATOM 2121 CD GLN G 422 88.821 −128.620 147.421 1.00 91.10 ATOM 2122 OE1 GLN G 422 89.614 −128.054 148.174 1.00 92.63 ATOM 2123 NE2 GLN G 422 87.527 −128.731 147.699 1.00 91.83 ATOM 2124 N ILE G 423 90.474 −126.706 142.493 1.00 79.69 ATOM 2125 CA ILE G 423 90.276 −125.734 141.431 1.00 79.70 ATOM 2126 C ILE G 423 91.021 −126.251 140.208 1.00 79.36 ATOM 2127 O ILE G 423 92.238 −126.436 140.240 1.00 81.30 ATOM 2128 CB ILE G 423 90.807 −124.356 141.858 1.00 79.75 ATOM 2129 CG1 ILE G 423 89.917 −123.811 142.982 1.00 80.64 ATOM 2130 CG2 ILE G 423 90.841 −123.411 140.668 1.00 79.15 ATOM 2131 CD1 ILE G 423 90.446 −122.563 143.643 1.00 83.89 ATOM 2132 N ILE G 424 90.275 −126.493 139.138 1.00 78.23 ATOM 2133 CA ILE G 424 90.833 −127.038 137.915 1.00 77.77 ATOM 2134 C ILE G 424 90.580 −126.185 136.690 1.00 77.60 ATOM 2135 O ILE G 424 89.543 −125.539 136.576 1.00 78.36 ATOM 2136 CB ILE G 424 90.208 −128.401 137.631 1.00 78.68 ATOM 2137 CG1 ILE G 424 90.294 −129.256 138.885 1.00 80.96 ATOM 2138 CG2 ILE G 424 90.893 −129.069 136.451 1.00 80.04 ATOM 2139 CD1 ILE G 424 89.310 −130.360 138.897 1.00 85.27 ATOM 2140 N ASN G 425 91.533 −126.182 135.766 1.00 78.21 ATOM 2141 CA ASN G 425 91.356 −125.444 134.521 1.00 79.38 ATOM 2142 C ASN G 425 90.717 −126.445 133.562 1.00 81.00 ATOM 2143 O ASN G 425 91.281 −127.506 133.291 1.00 82.92 ATOM 2144 CB ASN G 425 92.697 −124.946 133.978 1.00 78.48 ATOM 2145 CG ASN G 425 93.007 −123.526 134.408 1.00 79.22 ATOM 2146 OD1 ASN G 425 92.243 −122.601 134.123 1.00 78.79 ATOM 2147 ND2 ASN G 425 94.136 −123.341 135.080 1.00 80.19 ATOM 2148 N MET G 426 89.534 −126.112 133.057 1.00 82.44 ATOM 2149 CA MET G 426 88.803 −127.010 132.169 1.00 83.15 ATOM 2150 C MET G 426 89.441 −127.260 130.810 1.00 82.81 ATOM 2151 O MET G 426 89.996 −126.349 130.194 1.00 81.41 ATOM 2152 CB MET G 426 87.378 −126.496 131.982 1.00 84.29 ATOM 2153 CG MET G 426 86.668 −126.263 133.303 1.00 83.67 ATOM 2154 SD MET G 426 84.893 −126.182 133.114 1.00 83.84 ATOM 2155 CE MET G 426 84.500 −127.928 133.137 1.00 84.40 ATOM 2156 N TRP G 427 89.355 −128.509 130.353 1.00 82.00 ATOM 2157 CA TRP G 427 89.909 −128.910 129.063 1.00 81.18 ATOM 2158 C TRP G 427 88.857 −128.872 127.963 1.00 80.45 ATOM 2159 O TRP G 427 89.182 −128.678 126.793 1.00 80.26 ATOM 2160 CB TRP G 427 90.501 −130.323 129.142 1.00 81.81 ATOM 2161 CG TRP G 427 89.522 −131.397 129.531 1.00 82.28 ATOM 2162 CD1 TRP G 427 89.242 −131.834 130.794 1.00 82.98 ATOM 2163 CD2 TRP G 427 88.708 −132.181 128.646 1.00 81.40 ATOM 2164 NE1 TRP G 427 88.310 −132.843 130.751 1.00 82.68 ATOM 2165 CE2 TRP G 427 87.964 −133.076 129.447 1.00 81.58 ATOM 2166 CE3 TRP G 427 88.536 −132.213 127.256 1.00 80.71 ATOM 2167 CZ2 TRP G 427 87.061 −133.996 128.902 1.00 81.39 ATOM 2168 CZ3 TRP G 427 87.637 −133.130 126.715 1.00 80.74 ATOM 2169 CH2 TRP G 427 86.912 −134.007 127.539 1.00 80.83 ATOM 2170 N GLN G 428 87.596 −129.059 128.341 1.00 80.48 ATOM 2171 CA GLN G 428 86.509 −129.047 127.370 1.00 80.94 ATOM 2172 C GLN G 428 86.367 −127.664 126.752 1.00 80.28 ATOM 2173 O GLN G 428 86.432 −127.507 125.534 1.00 80.34 ATOM 2174 CB GLN G 428 85.192 −129.450 128.033 1.00 82.24 ATOM 2175 CG GLN G 428 85.271 −130.727 128.850 1.00 84.02 ATOM 2176 CD GLN G 428 85.490 −130.459 130.327 1.00 85.70 ATOM 2177 OE1 GLN G 428 86.450 −129.794 130.718 1.00 86.37 ATOM 2178 NE2 GLN G 428 84.593 −130.976 131.157 1.00 88.20 ATOM 2179 N GLU G 429 86.168 −126.661 127.599 1.00 79.28 ATOM 2180 CA GLU G 429 86.028 −125.290 127.128 1.00 79.36 ATOM 2181 C GLU G 429 86.891 −124.365 127.975 1.00 77.22 ATOM 2182 O GLU G 429 87.281 −124.718 129.088 1.00 77.49 ATOM 2183 CB GLU G 429 84.558 −124.850 127.196 1.00 82.15 ATOM 2184 CG GLU G 429 84.005 −124.666 128.603 1.00 82.38 ATOM 2185 CD GLU G 429 82.538 −124.263 128.606 1.00 83.05 ATOM 2186 OE1 GLU G 429 82.199 −123.225 127.998 1.00 81.83 ATOM 2187 OE2 GLU G 429 81.723 −124.988 129.215 1.00 83.79 ATOM 2188 N VAL G 430 87.199 −123.187 127.449 1.00 74.05 ATOM 2189 CA VAL G 430 88.009 −122.237 128.193 1.00 72.33 ATOM 2190 C VAL G 430 87.291 −121.876 129.491 1.00 72.05 ATOM 2191 O VAL G 430 86.126 −121.489 129.473 1.00 73.40 ATOM 2192 CB VAL G 430 88.240 −120.955 127.377 1.00 72.15 ATOM 2193 CG1 VAL G 430 89.157 −120.012 128.135 1.00 70.59 ATOM 2194 CG2 VAL G 430 88.826 −121.304 126.022 1.00 72.50 ATOM 2195 N GLY G 431 87.983 −122.013 130.616 1.00 71.44 ATOM 2196 CA GLY G 431 87.367 −121.693 131.891 1.00 70.65 ATOM 2197 C GLY G 431 87.947 −122.483 133.046 1.00 69.99 ATOM 2198 O GLY G 431 88.954 −123.168 132.884 1.00 72.09 ATOM 2199 N LYS G 432 87.319 −122.386 134.214 1.00 68.32 ATOM 2200 CA LYS G 432 87.785 −123.103 135.397 1.00 66.54 ATOM 2201 C LYS G 432 86.663 −123.912 136.026 1.00 64.43 ATOM 2202 O LYS G 432 85.510 −123.822 135.611 1.00 66.65 ATOM 2203 CB LYS G 432 88.344 −122.123 136.434 1.00 68.76 ATOM 2204 CG LYS G 432 89.580 −121.362 135.973 1.00 71.24 ATOM 2205 CD LYS G 432 90.008 −120.336 137.012 1.00 72.43 ATOM 2206 CE LYS G 432 91.167 −119.486 136.515 1.00 74.60 ATOM 2207 NZ LYS G 432 92.391 −120.287 136.230 1.00 76.20 ATOM 2208 N ALA G 433 87.008 −124.700 137.036 1.00 61.60 ATOM 2209 CA ALA G 433 86.031 −125.529 137.721 1.00 60.62 ATOM 2210 C ALA G 433 86.467 −125.778 139.156 1.00 61.66 ATOM 2211 O ALA G 433 87.655 −125.757 139.464 1.00 65.08 ATOM 2212 CB ALA G 433 85.872 −126.850 136.989 1.00 59.62 ATOM 2213 N MET G 434 85.495 −126.019 140.027 1.00 61.86 ATOM 2214 CA MET G 434 85.756 −126.272 141.439 1.00 62.17 ATOM 2215 C MET G 434 85.099 −127.572 141.885 1.00 63.75 ATOM 2216 O MET G 434 83.884 −127.727 141.762 1.00 65.83 ATOM 2217 CB MET G 434 85.203 −125.123 142.283 1.00 61.94 ATOM 2218 CG MET G 434 84.957 −125.495 143.737 1.00 62.90 ATOM 2219 SD MET G 434 86.262 −125.005 144.862 1.00 64.78 ATOM 2220 CE MET G 434 85.342 −123.924 145.974 1.00 64.90 ATOM 2221 N TYR G 435 85.890 −128.501 142.413 1.00 63.38 ATOM 2222 CA TYR G 435 85.343 −129.777 142.874 1.00 61.59 ATOM 2223 C TYR G 435 85.401 −129.929 144.388 1.00 62.48 ATOM 2224 O TYR G 435 86.030 −129.129 145.079 1.00 62.27 ATOM 2225 CB TYR G 435 86.079 −130.945 142.219 1.00 58.59 ATOM 2226 CG TYR G 435 85.750 −131.133 140.759 1.00 54.66 ATOM 2227 CD1 TYR G 435 86.207 −130.237 139.798 1.00 52.26 ATOM 2228 CD2 TYR G 435 84.967 −132.206 140.340 1.00 57.11 ATOM 2229 CE1 TYR G 435 85.893 −130.406 138.453 1.00 54.48 ATOM 2230 CE2 TYR G 435 84.646 −132.384 138.999 1.00 57.17 ATOM 2231 CZ TYR G 435 85.110 −131.482 138.062 1.00 55.72 ATOM 2232 OH TYR G 435 84.781 −131.663 136.738 1.00 55.13 ATOM 2233 N ALA G 436 84.747 −130.967 144.897 1.00 64.73 ATOM 2234 CA ALA G 436 84.713 −131.229 146.331 1.00 69.52 ATOM 2235 C ALA G 436 86.048 −131.755 146.862 1.00 73.34 ATOM 2236 O ALA G 436 86.882 −132.251 146.104 1.00 74.12 ATOM 2237 CB ALA G 436 83.598 −132.225 146.645 1.00 68.49 ATOM 2238 N PRO G 437 86.266 −131.648 148.184 1.00 77.56 ATOM 2239 CA PRO G 437 87.501 −132.114 148.818 1.00 80.89 ATOM 2240 C PRO G 437 87.721 −133.611 148.599 1.00 85.07 ATOM 2241 O PRO G 437 86.766 −134.365 148.413 1.00 86.90 ATOM 2242 CB PRO G 437 87.285 −131.754 150.285 1.00 79.74 ATOM 2243 CG PRO G 437 86.421 −130.527 150.197 1.00 78.93 ATOM 2244 CD PRO G 437 85.409 −130.972 149.171 1.00 77.85 ATOM 2245 N PRO G 438 88.988 −134.058 148.617 1.00 88.61 ATOM 2246 CA PRO G 438 89.362 −135.460 148.416 1.00 91.38 ATOM 2247 C PRO G 438 88.540 −136.458 149.225 1.00 95.06 ATOM 2248 O PRO G 438 88.062 −136.149 150.318 1.00 94.95 ATOM 2249 CB PRO G 438 90.840 −135.467 148.790 1.00 89.15 ATOM 2250 CG PRO G 438 91.284 −134.125 148.301 1.00 87.77 ATOM 2251 CD PRO G 438 90.189 −133.240 148.859 1.00 88.31 ATOM 2252 N ILE G 439 88.379 −137.655 148.672 1.00 99.51 ATOM 2253 CA ILE G 439 87.615 −138.713 149.320 1.00 105.19 ATOM 2254 C ILE G 439 88.361 −139.228 150.546 1.00 110.13 ATOM 2255 O ILE G 439 89.590 −139.212 150.581 1.00 110.70 ATOM 2256 CB ILE G 439 87.395 −139.884 148.354 1.00 104.20 ATOM 2257 CG1 ILE G 439 87.009 −139.347 146.973 1.00 103.55 ATOM 2258 CG2 ILE G 439 86.297 −140.795 148.882 1.00 104.68 ATOM 2259 CD1 ILE G 439 87.025 −140.395 145.894 1.00 105.15 ATOM 2260 N ARG G 440 87.613 −139.688 151.544 1.00 116.12 ATOM 2261 CA ARG G 440 88.200 −140.192 152.779 1.00 122.02 ATOM 2262 C ARG G 440 89.016 −141.478 152.623 1.00 124.42 ATOM 2263 O ARG G 440 90.028 −141.660 153.300 1.00 125.60 ATOM 2264 CB ARG G 440 87.096 −140.376 153.833 1.00 124.40 ATOM 2265 CG ARG G 440 85.821 −141.037 153.316 1.00 128.47 ATOM 2266 CD ARG G 440 85.962 −142.547 153.275 1.00 132.51 ATOM 2267 NE ARG G 440 85.509 −143.111 152.007 1.00 135.84 ATOM 2268 CZ ARG G 440 85.710 −144.374 151.643 1.00 137.31 ATOM 2269 NH1 ARG G 440 86.354 −145.200 152.456 1.00 137.16 ATOM 2270 NH2 ARG G 440 85.275 −144.810 150.467 1.00 136.49 ATOM 2271 N GLY G 441 88.592 −142.358 151.721 1.00 125.98 ATOM 2272 CA GLY G 441 89.305 −143.609 151.521 1.00 127.56 ATOM 2273 C GLY G 441 90.602 −143.502 150.739 1.00 128.74 ATOM 2274 O GLY G 441 91.025 −142.412 150.347 1.00 128.11 ATOM 2275 N GLN G 442 91.230 −144.653 150.518 1.00 129.91 ATOM 2276 CA GLN G 442 92.483 −144.745 149.780 1.00 130.78 ATOM 2277 C GLN G 442 92.234 −144.787 148.275 1.00 131.13 ATOM 2278 O GLN G 442 91.299 −145.438 147.805 1.00 130.50 ATOM 2279 CB GLN G 442 93.251 −145.997 150.219 1.00 132.26 ATOM 2280 CG GLN G 442 93.839 −146.801 149.072 1.00 134.25 ATOM 2281 CD GLN G 442 95.123 −147.506 149.454 1.00 135.13 ATOM 2282 OE1 GLN G 442 95.125 −148.447 150.248 1.00 136.02 ATOM 2283 NE2 GLN G 442 96.233 −147.040 148.897 1.00 134.96 ATOM 2284 N ILE G 443 93.084 −144.096 147.524 1.00 131.67 ATOM 2285 CA ILE G 443 92.961 −144.041 146.073 1.00 132.30 ATOM 2286 C ILE G 443 94.142 −144.725 145.398 1.00 131.73 ATOM 2287 O ILE G 443 95.271 −144.238 145.452 1.00 131.38 ATOM 2288 CB ILE G 443 92.890 −142.582 145.591 1.00 133.10 ATOM 2289 CG1 ILE G 443 91.729 −141.871 146.291 1.00 133.63 ATOM 2290 CG2 ILE G 443 92.701 −142.535 144.080 1.00 134.13 ATOM 2291 CD1 ILE G 443 91.703 −140.384 146.055 1.00 133.79 ATOM 2292 N ARG G 444 93.874 −145.856 144.759 1.00 131.74 ATOM 2293 CA ARG G 444 94.909 −146.629 144.078 1.00 131.48 ATOM 2294 C ARG G 444 94.593 −146.714 142.583 1.00 129.69 ATOM 2295 O ARG G 444 93.492 −147.113 142.205 1.00 129.68 ATOM 2296 CB ARG G 444 94.964 −148.037 144.693 1.00 133.90 ATOM 2297 CG ARG G 444 96.261 −148.390 145.433 1.00 136.43 ATOM 2298 CD ARG G 444 96.037 −149.515 146.449 1.00 138.19 ATOM 2299 NE ARG G 444 97.247 −150.283 146.748 1.00 139.51 ATOM 2300 CZ ARG G 444 98.290 −149.830 147.441 1.00 140.29 ATOM 2301 NH1 ARG G 444 98.294 −148.595 147.929 1.00 140.09 ATOM 2302 NH2 ARG G 444 99.338 −150.619 147.647 1.00 140.64 ATOM 2303 N CYS G 445 95.543 −146.334 141.732 1.00 127.32 ATOM 2304 CA CYS G 445 95.316 −146.391 140.286 1.00 124.83 ATOM 2305 C CYS G 445 96.544 −146.962 139.558 1.00 123.33 ATOM 2306 O CYS G 445 97.684 −146.679 139.926 1.00 123.02 ATOM 2307 CB CYS G 445 94.974 −144.987 139.740 1.00 124.31 ATOM 2308 SG CYS G 445 93.684 −144.087 140.680 1.00 124.41 ATOM 2309 N SER G 446 96.299 −147.780 138.536 1.00 121.97 ATOM 2310 CA SER G 446 97.366 −148.402 137.752 1.00 119.88 ATOM 2311 C SER G 446 97.031 −148.373 136.262 1.00 117.92 ATOM 2312 O SER G 446 95.924 −148.733 135.859 1.00 117.72 ATOM 2313 CB SER G 446 97.574 −149.853 138.202 1.00 120.03 ATOM 2314 OG SER G 446 96.407 −150.627 137.986 1.00 120.27 ATOM 2315 N SER G 447 97.994 −147.955 135.448 1.00 114.74 ATOM 2316 CA SER G 447 97.790 −147.875 134.008 1.00 112.04 ATOM 2317 C SER G 447 99.096 −148.079 133.241 1.00 108.70 ATOM 2318 O SER G 447 100.182 −147.987 133.812 1.00 108.62 ATOM 2319 CB SER G 447 97.173 −146.518 133.655 1.00 113.67 ATOM 2320 OG SER G 447 97.856 −145.468 134.314 1.00 114.63 ATOM 2321 N ASN G 448 98.975 −148.359 131.946 1.00 104.80 ATOM 2322 CA ASN G 448 100.127 −148.587 131.084 1.00 101.05 ATOM 2323 C ASN G 448 100.392 −147.407 130.161 1.00 98.08 ATOM 2324 O ASN G 448 99.549 −147.048 129.342 1.00 97.79 ATOM 2325 CB ASN G 448 99.908 −149.848 130.235 1.00 102.67 ATOM 2326 CG ASN G 448 100.039 −151.126 131.038 1.00 103.58 ATOM 2327 OD1 ASN G 448 101.140 −151.519 131.422 1.00 103.71 ATOM 2328 ND2 ASN G 448 98.912 −151.781 131.299 1.00 103.79 ATOM 2329 N ILE G 449 101.566 −146.804 130.294 1.00 94.94 ATOM 2330 CA ILE G 449 101.935 −145.676 129.449 1.00 92.96 ATOM 2331 C ILE G 449 102.228 −146.206 128.054 1.00 92.14 ATOM 2332 O ILE G 449 103.343 −146.635 127.757 1.00 91.85 ATOM 2333 CB ILE G 449 103.182 −144.975 129.987 1.00 93.15 ATOM 2334 CG1 ILE G 449 102.947 −144.584 131.449 1.00 94.25 ATOM 2335 CG2 ILE G 449 103.494 −143.747 129.141 1.00 91.79 ATOM 2336 CD1 ILE G 449 104.181 −144.084 132.146 1.00 94.95 ATOM 2337 N THR G 450 101.214 −146.178 127.201 1.00 91.70 ATOM 2338 CA THR G 450 101.349 −146.681 125.845 1.00 92.19 ATOM 2339 C THR G 450 101.910 −145.647 124.876 1.00 91.91 ATOM 2340 O THR G 450 102.164 −145.955 123.714 1.00 92.23 ATOM 2341 CB THR G 450 99.992 −147.171 125.312 1.00 92.87 ATOM 2342 OG1 THR G 450 99.044 −146.101 125.374 1.00 94.60 ATOM 2343 CG2 THR G 450 99.480 −148.328 126.147 1.00 91.70 ATOM 2344 N GLY G 451 102.101 −144.421 125.350 1.00 92.40 ATOM 2345 CA GLY G 451 102.631 −143.373 124.493 1.00 93.12 ATOM 2346 C GLY G 451 102.795 −142.059 125.232 1.00 93.74 ATOM 2347 O GLY G 451 102.551 −141.983 126.434 1.00 94.94 ATOM 2348 N LEU G 452 103.208 −141.020 124.516 1.00 93.32 ATOM 2349 CA LEU G 452 103.394 −139.708 125.121 1.00 94.48 ATOM 2350 C LEU G 452 103.370 −138.597 124.077 1.00 96.43 ATOM 2351 O LEU G 452 103.383 −138.862 122.875 1.00 97.24 ATOM 2352 CB LEU G 452 104.717 −139.660 125.898 1.00 94.99 ATOM 2353 CG LEU G 452 105.989 −140.116 125.174 1.00 94.35 ATOM 2354 CD1 LEU G 452 107.082 −139.061 125.305 1.00 93.41 ATOM 2355 CD2 LEU G 452 106.447 −141.441 125.767 1.00 94.53 ATOM 2356 N LEU G 453 103.339 −137.353 124.546 1.00 97.31 ATOM 2357 CA LEU G 453 103.312 −136.191 123.662 1.00 97.97 ATOM 2358 C LEU G 453 104.537 −135.317 123.900 1.00 99.02 ATOM 2359 O LEU G 453 104.923 −135.080 125.044 1.00 98.34 ATOM 2360 CB LEU G 453 102.045 −135.374 123.919 1.00 100.23 ATOM 2361 CG LEU G 453 100.710 −136.088 123.684 1.00 102.44 ATOM 2362 CD1 LEU G 453 99.780 −135.831 124.857 1.00 104.66 ATOM 2363 CD2 LEU G 453 100.089 −135.602 122.384 1.00 104.74 ATOM 2364 N LEU G 454 105.144 −134.835 122.821 1.00 101.32 ATOM 2365 CA LEU G 454 106.335 −133.995 122.925 1.00 104.16 ATOM 2366 C LEU G 454 106.287 −132.786 122.002 1.00 105.43 ATOM 2367 O LEU G 454 105.683 −132.829 120.935 1.00 104.92 ATOM 2368 CB LEU G 454 107.587 −134.810 122.590 1.00 107.11 ATOM 2369 CG LEU G 454 108.124 −135.787 123.640 1.00 109.52 ATOM 2370 CD1 LEU G 454 109.036 −136.808 122.980 1.00 110.38 ATOM 2371 CD2 LEU G 454 108.870 −135.011 124.718 1.00 110.90 ATOM 2372 N THR G 455 106.940 −131.710 122.423 1.00 107.87 ATOM 2373 CA THR G 455 107.007 −130.483 121.639 1.00 111.93 ATOM 2374 C THR G 455 108.450 −129.979 121.669 1.00 113.34 ATOM 2375 O THR G 455 108.941 −129.532 122.708 1.00 113.32 ATOM 2376 CB THR G 455 106.087 −129.392 122.216 1.00 112.59 ATOM 2377 OG1 THR G 455 106.172 −129.403 123.643 1.00 113.78 ATOM 2378 CG2 THR G 455 104.650 −129.615 121.796 1.00 113.67 ATOM 2379 N ARG G 456 109.126 −130.057 120.526 1.00 115.82 ATOM 2380 CA ARG G 456 110.520 −129.638 120.426 1.00 117.80 ATOM 2381 C ARG G 456 110.714 −128.126 120.336 1.00 118.96 ATOM 2382 O ARG G 456 109.853 −127.405 119.834 1.00 118.29 ATOM 2383 CB ARG G 456 111.177 −130.305 119.212 1.00 117.97 ATOM 2384 CG ARG G 456 110.748 −129.740 117.864 1.00 119.08 ATOM 2385 CD ARG G 456 111.533 −130.384 116.728 1.00 119.35 ATOM 2386 NE ARG G 456 111.439 −129.607 115.496 1.00 119.68 ATOM 2387 CZ ARG G 456 112.130 −128.496 115.257 1.00 119.75 ATOM 2388 NH1 ARG G 456 112.977 −128.027 116.165 1.00 120.37 ATOM 2389 NH2 ARG G 456 111.968 −127.847 114.112 1.00 119.93 ATOM 2390 N ASP G 457 111.860 −127.656 120.823 1.00 119.85 ATOM 2391 CA ASP G 457 112.189 −126.233 120.793 1.00 120.75 ATOM 2392 C ASP G 457 112.749 −125.857 119.427 1.00 122.23 ATOM 2393 O ASP G 457 113.723 −126.451 118.964 1.00 122.14 ATOM 2394 CB ASP G 457 113.226 −125.903 121.869 1.00 120.14 ATOM 2395 CG ASP G 457 112.739 −126.229 123.267 1.00 120.03 ATOM 2396 OD1 ASP G 457 113.374 −125.778 124.243 1.00 119.43 ATOM 2397 OD2 ASP G 457 111.721 −126.943 123.378 1.00 119.90 ATOM 2398 N GLY G 458 112.139 −124.865 118.787 1.00 123.91 ATOM 2399 CA GLY G 458 112.597 −124.440 117.475 1.00 126.39 ATOM 2400 C GLY G 458 113.689 −123.387 117.531 1.00 128.56 ATOM 2401 O GLY G 458 114.703 −123.567 118.205 1.00 128.30 ATOM 2402 N GLY G 459 113.487 −122.284 116.817 1.00 130.42 ATOM 2403 CA GLY G 459 114.472 −121.222 116.807 1.00 132.58 ATOM 2404 C GLY G 459 115.502 −121.403 115.712 1.00 134.70 ATOM 2405 O GLY G 459 116.070 −122.485 115.552 1.00 134.58 ATOM 2406 N ILE G 460 115.751 −120.338 114.959 1.00 137.83 ATOM 2407 CA ILE G 460 116.726 −120.379 113.875 1.00 140.76 ATOM 2408 C ILE G 460 118.138 −120.321 114.468 1.00 142.81 ATOM 2409 O ILE G 460 119.123 −120.606 113.792 1.00 142.92 ATOM 2410 CB ILE G 460 116.497 −119.194 112.903 1.00 140.96 ATOM 2411 CG1 ILE G 460 116.933 −119.570 111.484 1.00 141.22 ATOM 2412 CG2 ILE G 460 117.259 −117.970 113.383 1.00 141.19 ATOM 2413 CD1 ILE G 460 118.421 −119.766 111.310 1.00 140.88 ATOM 2414 N ASN G 461 118.223 −119.963 115.746 1.00 145.09 ATOM 2415 CA ASN G 461 119.506 −119.878 116.443 1.00 147.66 ATOM 2416 C ASN G 461 120.070 −121.289 116.632 1.00 149.02 ATOM 2417 O ASN G 461 119.393 −122.161 117.178 1.00 148.11 ATOM 2418 CB ASN G 461 119.309 −119.186 117.800 1.00 148.39 ATOM 2419 CG ASN G 461 120.581 −118.560 118.329 1.00 149.53 ATOM 2420 OD1 ASN G 461 121.509 −119.257 118.737 1.00 149.19 ATOM 2421 ND2 ASN G 461 120.631 −117.233 118.323 1.00 148.79 ATOM 2422 N GLU G 462 121.303 −121.511 116.179 1.00 151.28 ATOM 2423 CA GLU G 462 121.931 −122.826 116.284 1.00 153.22 ATOM 2424 C GLU G 462 122.706 −123.073 117.578 1.00 153.57 ATOM 2425 O GLU G 462 123.216 −122.143 118.202 1.00 153.46 ATOM 2426 CB GLU G 462 122.859 −123.067 115.085 1.00 153.86 ATOM 2427 CG GLU G 462 124.074 −122.139 114.989 1.00 156.71 ATOM 2428 CD GLU G 462 123.763 −120.798 114.342 1.00 157.61 ATOM 2429 OE1 GLU G 462 123.171 −119.922 115.006 1.00 157.89 ATOM 2430 OE2 GLU G 462 124.110 −120.625 113.154 1.00 158.13 ATOM 2431 N ASN G 463 122.794 −124.342 117.965 1.00 153.66 ATOM 2432 CA ASN G 463 123.507 −124.735 119.172 1.00 153.40 ATOM 2433 C ASN G 463 123.918 −126.200 119.044 1.00 152.49 ATOM 2434 O ASN G 463 124.772 −126.690 119.784 1.00 152.48 ATOM 2435 CB ASN G 463 122.608 −124.525 120.400 1.00 154.12 ATOM 2436 CG ASN G 463 123.375 −124.598 121.707 1.00 155.58 ATOM 2437 OD1 ASN G 463 123.613 −125.679 122.245 1.00 156.54 ATOM 2438 ND2 ASN G 463 123.780 −123.439 122.217 1.00 156.41 ATOM 2439 N GLY G 464 123.311 −126.886 118.081 1.00 150.94 ATOM 2440 CA GLY G 464 123.614 −128.286 117.858 1.00 149.00 ATOM 2441 C GLY G 464 122.693 −129.184 118.658 1.00 147.53 ATOM 2442 O GLY G 464 122.652 −130.397 118.450 1.00 147.66 ATOM 2443 N THR G 465 121.937 −128.577 119.566 1.00 145.51 ATOM 2444 CA THR G 465 121.012 −129.311 120.416 1.00 142.98 ATOM 2445 C THR G 465 119.561 −128.931 120.146 1.00 140.93 ATOM 2446 O THR G 465 119.208 −127.752 120.074 1.00 140.82 ATOM 2447 CB THR G 465 121.305 −129.042 121.903 1.00 143.71 ATOM 2448 OG1 THR G 465 121.216 −127.633 122.153 1.00 144.71 ATOM 2449 CG2 THR G 465 122.691 −129.520 122.266 1.00 143.31 ATOM 2450 N GLU G 466 118.730 −129.951 119.981 1.00 137.84 ATOM 2451 CA GLU G 466 117.304 −129.762 119.750 1.00 134.60 ATOM 2452 C GLU G 466 116.586 −130.315 120.976 1.00 132.23 ATOM 2453 O GLU G 466 116.495 −131.530 121.155 1.00 131.65 ATOM 2454 CB GLU G 466 116.866 −130.515 118.492 1.00 134.81 ATOM 2455 CG GLU G 466 117.430 −129.969 117.182 1.00 135.55 ATOM 2456 CD GLU G 466 116.756 −128.681 116.729 1.00 136.34 ATOM 2457 OE1 GLU G 466 117.195 −128.100 115.711 1.00 136.05 ATOM 2458 OE2 GLU G 466 115.785 −128.250 117.386 1.00 137.26 ATOM 2459 N ILE G 467 116.080 −129.417 121.814 1.00 129.25 ATOM 2460 CA ILE G 467 115.400 −129.801 123.047 1.00 126.01 ATOM 2461 C ILE G 467 113.989 −130.338 122.826 1.00 123.54 ATOM 2462 O ILE G 467 113.261 −129.848 121.966 1.00 122.31 ATOM 2463 CB ILE G 467 115.299 −128.602 124.008 1.00 125.82 ATOM 2464 CG1 ILE G 467 116.509 −127.686 123.827 1.00 125.39 ATOM 2465 CG2 ILE G 467 115.262 −129.091 125.449 1.00 124.63 ATOM 2466 CD1 ILE G 467 117.829 −128.361 124.104 1.00 125.46 ATOM 2467 N PHE G 468 113.609 −131.345 123.610 1.00 121.29 ATOM 2468 CA PHE G 468 112.277 −131.939 123.518 1.00 119.38 ATOM 2469 C PHE G 468 111.562 −131.923 124.866 1.00 117.84 ATOM 2470 O PHE G 468 111.904 −132.687 125.768 1.00 118.28 ATOM 2471 CB PHE G 468 112.360 −133.382 123.005 1.00 119.43 ATOM 2472 CG PHE G 468 112.625 −133.488 121.533 1.00 119.45 ATOM 2473 CD1 PHE G 468 113.909 −133.319 121.028 1.00 119.08 ATOM 2474 CD2 PHE G 468 111.584 −133.738 120.645 1.00 119.65 ATOM 2475 CE1 PHE G 468 114.154 −133.397 119.660 1.00 119.36 ATOM 2476 CE2 PHE G 468 111.818 −133.817 119.274 1.00 119.82 ATOM 2477 CZ PHE G 468 113.105 −133.647 118.781 1.00 119.73 ATOM 2478 N ARG G 469 110.564 −131.053 124.991 1.00 115.90 ATOM 2479 CA ARG G 469 109.789 −130.924 126.224 1.00 113.44 ATOM 2480 C ARG G 469 108.427 −131.610 126.079 1.00 112.22 ATOM 2481 O ARG G 469 107.896 −131.719 124.975 1.00 112.65 ATOM 2482 CB ARG G 469 109.598 −129.441 126.557 1.00 113.09 ATOM 2483 CG ARG G 469 110.898 −128.670 126.770 1.00 111.90 ATOM 2484 CD ARG G 469 110.656 −127.167 126.817 1.00 111.27 ATOM 2485 NE ARG G 469 111.891 −126.413 127.024 1.00 110.94 ATOM 2486 CZ ARG G 469 112.337 −126.009 128.210 1.00 111.59 ATOM 2487 NH1 ARG G 469 111.650 −126.282 129.311 1.00 111.63 ATOM 2488 NH2 ARG G 469 113.474 −125.331 128.297 1.00 111.19 ATOM 2489 N PRO G 470 107.846 −132.080 127.196 1.00 110.32 ATOM 2490 CA PRO G 470 106.544 −132.757 127.180 1.00 109.56 ATOM 2491 C PRO G 470 105.415 −131.804 126.802 1.00 109.38 ATOM 2492 O PRO G 470 105.184 −130.810 127.487 1.00 109.40 ATOM 2493 CB PRO G 470 106.404 −133.268 128.615 1.00 108.27 ATOM 2494 CG PRO G 470 107.830 −133.391 129.083 1.00 109.61 ATOM 2495 CD PRO G 470 108.422 −132.120 128.547 1.00 110.06 ATOM 2496 N GLY G 471 104.716 −132.104 125.712 1.00 109.49 ATOM 2497 CA GLY G 471 103.619 −131.252 125.285 1.00 109.11 ATOM 2498 C GLY G 471 102.315 −131.685 125.924 1.00 108.92 ATOM 2499 O GLY G 471 102.257 −131.939 127.126 1.00 108.60 ATOM 2500 N GLY G 472 101.265 −131.772 125.119 1.00 109.42 ATOM 2501 CA GLY G 472 99.979 −132.193 125.638 1.00 110.45 ATOM 2502 C GLY G 472 99.070 −131.040 126.004 1.00 111.45 ATOM 2503 O GLY G 472 99.502 −129.891 126.097 1.00 111.96 ATOM 2504 N GLY G 473 97.796 −131.351 126.209 1.00 111.01 ATOM 2505 CA GLY G 473 96.835 −130.322 126.562 1.00 110.43 ATOM 2506 C GLY G 473 95.576 −130.471 125.741 1.00 109.88 ATOM 2507 O GLY G 473 94.491 −130.678 126.277 1.00 109.70 ATOM 2508 N ASP G 474 95.730 −130.366 124.428 1.00 109.83 ATOM 2509 CA ASP G 474 94.608 −130.513 123.516 1.00 110.37 ATOM 2510 C ASP G 474 94.250 −131.993 123.454 1.00 110.43 ATOM 2511 O ASP G 474 95.003 −132.796 122.907 1.00 110.70 ATOM 2512 CB ASP G 474 94.996 −129.990 122.135 1.00 111.19 ATOM 2513 CG ASP G 474 93.885 −130.137 121.121 1.00 111.06 ATOM 2514 OD1 ASP G 474 92.726 −129.834 121.465 1.00 110.92 ATOM 2515 OD2 ASP G 474 94.180 −130.541 119.977 1.00 111.81 ATOM 2516 N MET G 475 93.102 −132.346 124.024 1.00 109.99 ATOM 2517 CA MET G 475 92.659 −133.732 124.061 1.00 108.99 ATOM 2518 C MET G 475 92.325 −134.343 122.706 1.00 108.30 ATOM 2519 O MET G 475 91.989 −135.524 122.634 1.00 108.27 ATOM 2520 CB MET G 475 91.454 −133.873 124.992 1.00 110.06 ATOM 2521 CG MET G 475 91.742 −133.498 126.443 1.00 110.69 ATOM 2522 SD MET G 475 93.014 −134.548 127.161 1.00 111.79 ATOM 2523 CE MET G 475 93.387 −133.671 128.688 1.00 111.72 ATOM 2524 N ARG G 476 92.409 −133.560 121.633 1.00 107.84 ATOM 2525 CA ARG G 476 92.113 −134.093 120.302 1.00 107.39 ATOM 2526 C ARG G 476 93.218 −135.060 119.904 1.00 105.79 ATOM 2527 O ARG G 476 92.979 −136.056 119.224 1.00 105.68 ATOM 2528 CB ARG G 476 92.034 −132.961 119.271 1.00 108.90 ATOM 2529 CG ARG G 476 90.927 −131.951 119.512 1.00 110.95 ATOM 2530 CD ARG G 476 91.060 −130.754 118.578 1.00 112.58 ATOM 2531 NE ARG G 476 90.086 −129.707 118.883 1.00 114.24 ATOM 2532 CZ ARG G 476 90.079 −128.499 118.323 1.00 115.25 ATOM 2533 NH1 ARG G 476 90.997 −128.170 117.422 1.00 114.91 ATOM 2534 NH2 ARG G 476 89.151 −127.616 118.668 1.00 115.36 ATOM 2535 N ASP G 477 94.430 −134.748 120.345 1.00 103.73 ATOM 2536 CA ASP G 477 95.599 −135.558 120.051 1.00 101.54 ATOM 2537 C ASP G 477 95.552 −136.903 120.752 1.00 99.60 ATOM 2538 O ASP G 477 96.155 −137.864 120.286 1.00 98.87 ATOM 2539 CB ASP G 477 96.863 −134.813 120.473 1.00 103.36 ATOM 2540 CG ASP G 477 96.918 −133.399 119.918 1.00 105.17 ATOM 2541 OD1 ASP G 477 96.905 −133.252 118.680 1.00 105.96 ATOM 2542 OD2 ASP G 477 96.965 −132.441 120.720 1.00 106.74 ATOM 2543 N ASN G 478 94.844 −136.972 121.875 1.00 98.58 ATOM 2544 CA ASN G 478 94.741 −138.220 122.628 1.00 98.61 ATOM 2545 C ASN G 478 93.974 −139.286 121.862 1.00 99.30 ATOM 2546 O ASN G 478 94.303 −140.468 121.926 1.00 99.94 ATOM 2547 CB ASN G 478 94.058 −137.984 123.977 1.00 97.49 ATOM 2548 CG ASN G 478 94.911 −137.180 124.928 1.00 96.81 ATOM 2549 OD1 ASN G 478 95.228 −136.022 124.666 1.00 95.84 ATOM 2550 ND2 ASN G 478 95.289 −137.792 126.044 1.00 97.25 ATOM 2551 N TRP G 479 92.945 −138.861 121.141 1.00 99.87 ATOM 2552 CA TRP G 479 92.131 −139.788 120.370 1.00 100.66 ATOM 2553 C TRP G 479 92.738 −139.936 118.980 1.00 102.34 ATOM 2554 O TRP G 479 92.442 −140.887 118.259 1.00 102.87 ATOM 2555 CB TRP G 479 90.692 −139.267 120.263 1.00 98.97 ATOM 2556 CG TRP G 479 90.253 −138.426 121.434 1.00 96.33 ATOM 2557 CD1 TRP G 479 89.768 −137.150 121.384 1.00 94.67 ATOM 2558 CD2 TRP G 479 90.275 −138.791 122.823 1.00 94.42 ATOM 2559 NE1 TRP G 479 89.491 −136.696 122.651 1.00 92.78 ATOM 2560 CE2 TRP G 479 89.795 −137.680 123.553 1.00 92.98 ATOM 2561 CE3 TRP G 479 90.660 −139.944 123.520 1.00 93.84 ATOM 2562 CZ2 TRP G 479 89.681 −137.691 124.948 1.00 92.68 ATOM 2563 CZ3 TRP G 479 90.547 −139.954 124.910 1.00 93.85 ATOM 2564 CH2 TRP G 479 90.063 −138.831 125.606 1.00 93.88 ATOM 2565 N ARG G 480 93.588 −138.984 118.607 1.00 103.86 ATOM 2566 CA ARG G 480 94.246 −139.015 117.304 1.00 105.08 ATOM 2567 C ARG G 480 95.281 −140.125 117.271 1.00 105.26 ATOM 2568 O ARG G 480 95.594 −140.668 116.215 1.00 105.84 ATOM 2569 CB ARG G 480 94.922 −137.670 117.013 1.00 106.56 ATOM 2570 CG ARG G 480 94.125 −136.768 116.090 1.00 107.60 ATOM 2571 CD ARG G 480 94.632 −135.333 116.100 1.00 109.95 ATOM 2572 NE ARG G 480 93.740 −134.452 115.346 1.00 114.38 ATOM 2573 CZ ARG G 480 93.766 −133.122 115.392 1.00 117.10 ATOM 2574 NH1 ARG G 480 94.645 −132.492 116.162 1.00 118.14 ATOM 2575 NH2 ARG G 480 92.901 −132.421 114.671 1.00 119.32 ATOM 2576 N SER G 481 95.807 −140.461 118.440 1.00 105.09 ATOM 2577 CA SER G 481 96.810 −141.506 118.545 1.00 105.78 ATOM 2578 C SER G 481 96.169 −142.872 118.346 1.00 106.98 ATOM 2579 O SER G 481 96.853 −143.854 118.069 1.00 107.51 ATOM 2580 CB SER G 481 97.483 −141.448 119.918 1.00 105.86 ATOM 2581 OG SER G 481 96.531 −141.636 120.949 1.00 102.63 ATOM 2582 N GLU G 482 94.850 −142.925 118.487 1.00 108.44 ATOM 2583 CA GLU G 482 94.112 −144.173 118.341 1.00 110.31 ATOM 2584 C GLU G 482 93.359 −144.249 117.016 1.00 111.16 ATOM 2585 O GLU G 482 93.213 −145.324 116.438 1.00 111.61 ATOM 2586 CB GLU G 482 93.123 −144.327 119.501 1.00 110.81 ATOM 2587 CG GLU G 482 93.759 −144.254 120.883 1.00 110.72 ATOM 2588 CD GLU G 482 94.577 −145.485 121.225 1.00 110.51 ATOM 2589 OE1 GLU G 482 93.977 −146.563 121.425 1.00 109.50 ATOM 2590 OE2 GLU G 482 95.819 −145.375 121.292 1.00 110.56 ATOM 2591 N LEU G 483 92.883 −143.103 116.540 1.00 111.84 ATOM 2592 CA LEU G 483 92.130 −143.046 115.294 1.00 112.60 ATOM 2593 C LEU G 483 92.979 −142.608 114.107 1.00 113.68 ATOM 2594 O LEU G 483 92.449 −142.122 113.108 1.00 114.27 ATOM 2595 CB LEU G 483 90.949 −142.083 115.440 1.00 112.17 ATOM 2596 CG LEU G 483 89.872 −142.442 116.469 1.00 111.13 ATOM 2597 CD1 LEU G 483 88.927 −141.266 116.650 1.00 110.76 ATOM 2598 CD2 LEU G 483 89.115 −143.677 116.003 1.00 111.73 ATOM 2599 N TYR G 484 94.292 −142.782 114.206 1.00 114.79 ATOM 2600 CA TYR G 484 95.186 −142.383 113.125 1.00 115.54 ATOM 2601 C TYR G 484 95.019 −143.284 111.912 1.00 115.88 ATOM 2602 O TYR G 484 95.102 −142.827 110.774 1.00 115.90 ATOM 2603 CB TYR G 484 96.644 −142.409 113.602 1.00 115.90 ATOM 2604 CG TYR G 484 97.250 −143.791 113.733 1.00 116.80 ATOM 2605 CD1 TYR G 484 98.038 −144.328 112.714 1.00 116.77 ATOM 2606 CD2 TYR G 484 97.042 −144.560 114.878 1.00 118.01 ATOM 2607 CE1 TYR G 484 98.608 −145.597 112.836 1.00 117.84 ATOM 2608 CE2 TYR G 484 97.606 −145.828 115.008 1.00 118.60 ATOM 2609 CZ TYR G 484 98.388 −146.339 113.985 1.00 118.39 ATOM 2610 OH TYR G 484 98.956 −147.587 114.115 1.00 118.31 ATOM 2611 N LYS G 485 94.780 −144.566 112.160 1.00 116.57 ATOM 2612 CA LYS G 485 94.606 −145.525 111.082 1.00 117.94 ATOM 2613 C LYS G 485 93.136 −145.765 110.752 1.00 119.33 ATOM 2614 O LYS G 485 92.749 −146.883 110.413 1.00 119.55 ATOM 2615 CB LYS G 485 95.282 −146.851 111.451 1.00 116.62 ATOM 2616 CG LYS G 485 94.855 −147.425 112.794 1.00 114.79 ATOM 2617 CD LYS G 485 95.577 −148.736 113.075 1.00 113.85 ATOM 2618 CE LYS G 485 95.207 −149.299 114.438 1.00 112.32 ATOM 2619 NZ LYS G 485 95.894 −150.593 114.708 1.00 112.53 ATOM 2620 N TYR G 486 92.321 −144.718 110.849 1.00 121.24 ATOM 2621 CA TYR G 486 90.895 −144.831 110.549 1.00 123.65 ATOM 2622 C TYR G 486 90.356 −143.638 109.763 1.00 125.80 ATOM 2623 O TYR G 486 90.761 −142.499 109.986 1.00 126.52 ATOM 2624 CB TYR G 486 90.077 −144.979 111.836 1.00 122.26 ATOM 2625 CG TYR G 486 90.279 −146.286 112.559 1.00 120.89 ATOM 2626 CD1 TYR G 486 91.272 −146.426 113.527 1.00 120.39 ATOM 2627 CD2 TYR G 486 89.478 −147.389 112.271 1.00 120.13 ATOM 2628 CE1 TYR G 486 91.461 −147.636 114.192 1.00 119.39 ATOM 2629 CE2 TYR G 486 89.660 −148.600 112.927 1.00 119.78 ATOM 2630 CZ TYR G 486 90.651 −148.717 113.885 1.00 119.20 ATOM 2631 OH TYR G 486 90.829 −149.916 114.531 1.00 118.81 ATOM 2632 N LYS G 487 89.433 −143.912 108.848 1.00 127.78 ATOM 2633 CA LYS G 487 88.820 −142.869 108.041 1.00 129.98 ATOM 2634 C LYS G 487 87.421 −143.315 107.641 1.00 131.14 ATOM 2635 O LYS G 487 87.261 −144.328 106.959 1.00 131.65 ATOM 2636 CB LYS G 487 89.660 −142.592 106.786 1.00 130.89 ATOM 2637 CG LYS G 487 89.250 −141.325 106.044 1.00 132.86 ATOM 2638 CD LYS G 487 90.086 −141.091 104.791 1.00 134.47 ATOM 2639 CE LYS G 487 89.712 −139.769 104.131 1.00 134.86 ATOM 2640 NZ LYS G 487 90.540 −139.468 102.931 1.00 133.70 ATOM 2641 N VAL G 488 86.408 −142.571 108.072 1.00 132.54 ATOM 2642 CA VAL G 488 85.031 −142.915 107.737 1.00 134.39 ATOM 2643 C VAL G 488 84.808 −142.655 106.245 1.00 135.42 ATOM 2644 O VAL G 488 85.382 −141.719 105.682 1.00 135.33 ATOM 2645 CB VAL G 488 84.047 −142.072 108.571 1.00 134.46 ATOM 2646 CG1 VAL G 488 84.146 −140.608 108.170 1.00 134.65 ATOM 2647 CG2 VAL G 488 82.638 −142.599 108.401 1.00 134.22 ATOM 2648 N VAL G 489 83.982 −143.470 105.600 1.00 137.04 ATOM 2649 CA VAL G 489 83.762 −143.293 104.173 1.00 139.05 ATOM 2650 C VAL G 489 82.330 −143.585 103.707 1.00 140.08 ATOM 2651 O VAL G 489 81.606 −144.357 104.338 1.00 140.02 ATOM 2652 CB VAL G 489 84.732 −144.207 103.383 1.00 139.34 ATOM 2653 CG1 VAL G 489 83.998 −145.432 102.860 1.00 140.18 ATOM 2654 CG2 VAL G 489 85.385 −143.422 102.267 1.00 139.74 ATOM 2655 N LYS G 490 81.934 −142.966 102.597 1.00 142.79 ATOM 2656 CA LYS G 490 80.607 −143.179 102.032 1.00 145.45 ATOM 2657 C LYS G 490 80.669 −144.502 101.281 1.00 147.18 ATOM 2658 O LYS G 490 81.655 −144.786 100.598 1.00 146.18 ATOM 2659 CB LYS G 490 80.247 −142.036 101.070 1.00 145.83 ATOM 2660 CG LYS G 490 78.752 −141.852 100.807 1.00 146.99 ATOM 2661 CD LYS G 490 78.501 −140.629 99.928 1.00 148.09 ATOM 2662 CE LYS G 490 77.034 −140.213 99.934 1.00 148.60 ATOM 2663 NZ LYS G 490 76.795 −138.971 99.143 1.00 149.62 ATOM 2664 N ILE G 491 79.626 −145.312 101.399 1.00 149.88 ATOM 2665 CA ILE G 491 79.617 −146.604 100.731 1.00 153.14 ATOM 2666 C ILE G 491 79.546 −146.484 99.202 1.00 154.50 ATOM 2667 O ILE G 491 78.688 −147.084 98.550 1.00 154.54 ATOM 2668 CB ILE G 491 78.451 −147.475 101.262 1.00 153.49 ATOM 2669 CG1 ILE G 491 78.722 −148.946 100.955 1.00 154.55 ATOM 2670 CG2 ILE G 491 77.126 −147.000 100.685 1.00 153.61 ATOM 2671 CD1 ILE G 491 79.857 −149.529 101.778 1.00 154.67 ATOM 2672 N GLU G 492 80.465 −145.699 98.645 1.00 156.47 ATOM 2673 CA GLU G 492 80.561 −145.474 97.201 1.00 158.38 ATOM 2674 C GLU G 492 81.994 −145.101 96.827 1.00 159.02 ATOM 2675 O GLU G 492 82.890 −145.919 97.028 1.00 158.59 ATOM 2676 CB GLU G 492 79.624 −144.345 96.762 1.00 159.61 ATOM 2677 CG GLU G 492 78.521 −144.781 95.808 1.00 162.25 ATOM 2678 CD GLU G 492 77.654 −143.621 95.352 1.00 162.67 ATOM 2679 OE1 GLU G 492 78.173 −142.729 94.645 1.00 163.05 ATOM 2680 OE2 GLU G 492 76.455 −143.599 95.704 1.00 162.15 ATOM 2681 OXT GLU G 492 82.208 −143.994 96.336 1.00 158.19 TER 2682 GLU G 492 END

The present disclosure also provides for a machine-readable data storage medium which comprises a data storage material encoded with machine readable data defined by the structure coordinates of a stabilized gp120 polypeptide or gp120 polypeptide with an extended V3 loop as define in Table 1 or Table 2 respectively, or a subset thereof, such as at least about 5, such at least about 10, at least about 20, at least about 30, at least at least about 40, at least about 50, at least about 60, at least about 70, at least about 80, at least about 90, at least about 100, at least about 150, at least about 200, at least about 250, at least about 300, at least about 350, at least about 400, at least about 450, at least about 500 or more atoms of the structure, such as defined by the coordinates of Table 1 or Table 2.

Those of skill in the art will understand that a set of structure coordinates for a gp120 polypeptide, for example a stabilized gp120 polypeptide, a gp120 polypeptide with an extended V3 loop, or a portion thereof, is a relative set of points that define a shape in three dimensions. Thus, it is possible that an entirely different set of coordinates could define a similar or identical shape. Moreover, slight variations in the individual coordinates will have little effect on overall shape. The variations in coordinates discussed above may be generated because of mathematical manipulations of the structure coordinates. For example, the structure coordinates set forth in Table 1 or Table 2, or a portion thereof could be manipulated by crystallographic permutations of the structure coordinates, fractionalization of the structure coordinates; integer additions or subtractions to sets of the structure coordinates, deletion of a portion of the coordinates, inversion of the structure coordinates, or any combination of the above.

This disclosure further provides systems, such as computer systems, intended to generate structures and/or perform rational drug or compound design for an antigenic compound capable of eliciting an immune response in a subject. The system can contain one or more or all of: atomic co-ordinate data according to Table 1, Table 2, or a subset thereof and the Figures derived therefrom by homology modeling, the data defining the three-dimensional structure of a gp120 or at least one sub-domain thereof, or structure factor data for gp120, the structure factor data being derivable from the atomic co-ordinate data of Table 1 or Table 2 or a subset thereof and the Figures. This disclosure also involves computer readable media with: atomic co-ordinate data according to Table 1, Table 2 or a subset thereof and/or the Figures or derived therefrom by homology modeling, the data defining the three-dimensional structure of a gp120 or at least one sub-domain thereof; or structure factor data for a gp120, the structure factor data being derivable from the atomic co-ordinate data of Table 1, Table 2, or a subset thereof and/or the Figures. By providing such computer readable media, the atomic co-ordinate data can be routinely accessed to the gp120 or a sub-domain thereof. For example RASMOL (Sayle et al., TIBS vol. 20 (1995), 374) is a publicly available software package which allows access and analysis of atomic co-ordinate data for structural determination and/or rational drug design. Structure factor data, which are derivable from atomic co-ordinate data (see, for example, Blundell et al., in Protein Crystallography, Academic Press, NY, London and San Francisco (1976)), are particularly useful for calculating electron density maps, for example, difference Fourier electron density maps. Thus, there are additional uses for the computer readable media and/or computer systems and/or atomic co-ordinate data and additional reasons to provide them to users.

VIII. Identification of Immunogens

The crystals of this disclosure and particularly the atomic structure coordinates obtained from these crystals are particularly useful for identifying compounds elicit neutralizing antibodies, for example CD4BS and CD4i antibodies. The compounds identified are useful in eliciting antibodies to gp120, such as antibodies to lentivirus, such as SIV, or HIV, for example HIV-1 or HIV-2.

The crystal structure of a stabilized form of gp120 or a gp120 with the V3 loop in the extended conformation allows a novel approach for drug or compound discovery, identification, and design of compounds that mimic the antigenic surfaces of gp120 that bind neutralizing antibodies. Such compound can be useful as immunogens to illicit an immune response to HIV when administered to a subject, for example by eliciting anti-HIV antibodies, such as neutralizing antibodies, for example CD4BD or CD4i antibodies. Compounds that elicit anti-HIV antibodies are useful in diagnosis, treatment, or prevention of HIV-1 in a subject in need thereof.

The disclosure provides a computer-based method of rational drug, compound design, or identification which comprises: providing the structure of a stabilized form of gp120 (for example as defined by the coordinates or a subset of the coordinates in Table 1 and/or in the Figures) or a gp120 with the V3 loop in the extended conformation (for example as defined by the coordinates or subset of the coordinates in Table 2 and/or in the Figures); providing a structure of a candidate compound; and fitting the structure of the candidate compound to the structure of the stabilized form of gp120 (for example as defined by the coordinates or a subset of the coordinates in Table 1 and/or in the Figures) or the gp120 with the V3 loop in the extended conformation (for example as defined by the coordinates or a subset of the coordinates in Table 2 and/or in the Figures.

In certain embodiments, the coordinates of atoms of interest of the stabilized form of gp120 or the gp120 with the V3 loop in the extended conformation in the vicinity of the antigenic surface are used to model the antigenic surface to which as antibody binds, such as a neutralizing antibody, for example a CD4i or CD4BS antibody. These coordinates may be used to define a space which is then screened “in silico” against a candidate compound. Thus, the disclosure provides a computer-based method of rational drug or compound design or identification which comprises: providing the coordinates of at least two atoms of Table 1 or Table 2; providing the structure of a candidate compound; and fitting the structure of the candidate to the coordinates of at least two atoms of Table 1 or Table 2.

In practice, it may be desirable to model a sufficient number of atoms of the stabilized form of gp120 or the gp120 with the V3 loop in the extended conformation as defined by the coordinates of Table 1 or Table 2 which represent the active site or binding region. Thus, there can be provided the coordinates of at least about 5, such at least about 10, at least about 20, at least about 30, at least at least about 40, at least about 50, at least about 60, at least about 70, at least about 80, at least about 90, at least about 100, at least about 150, at least about 200, at least about 250, at least about 300, at least about 350, at least about 400, at least about 450, or at least about 500 atoms of the structure.

The methods disclosed herein can employ a sub-domain, region, or fragment of interest of the stabilized form of gp120 or the gp120 with the extended V3 loop which is in the vicinity of the antigenic surface, and providing a computer-based method for identifying or rationally designing a compound or drug, such as an immunogen which includes: providing the coordinates of at least a sub-domain, region, or fragment of the stabilized form of gp120 or the gp120 with the extended V3 loop; providing the structure of a candidate compound that mimics the antigenic surface of the gp120 with the extended V3 loop; and fitting the structure of the candidate compound to the coordinates of the stabilized form of gp120 or the gp120 with the extended V3 loop sub-domain, region, or fragment provided. A “sub-domain”, “region”, or “fragment” can mean at least one, for example, one, two, three, four, or more, element(s) of secondary structure of particular regions of the stabilized form of gp120 or the gp120 with the extended V3 loop gp120 with the extended V3 loop, and includes those set forth in Table 1 and Table 2.

These methods can optionally include synthesizing the candidate compound, (such as an immunogen) and/or administering the candidate compound to an animal capable of eliciting antibodies and testing whether the candidate compound elicits anti-HIV antibodies. Compounds which elicit anti-HIV antibodies are useful for diagnostic purposes, as well as for immunogenic, immunological or even vaccine compositions, as well as pharmaceutical compositions.

In some embodiments, the candidate compound is designed from the gp120 amino acid sequence, for example an amino acid sequence is assembled to provide a candidate compound, for example by synthesizing the amino acid sequence or producing a nucleic acid encoding the candidate compound.

The step of providing the structure of a candidate compound may involve selecting the candidate compound by computationally screening a database of compounds for surface similarity with an epitope on the stabilized form of gp120 or the gp120 with the extended V3 loop. For example, a 3-D descriptor for the candidate compound may be derived, the descriptor including geometric and functional constraints derived from the architecture and chemical nature of the epitope. The descriptor may then be used to interrogate the compound database, a candidate compound being a compound that has a good match to the features of the descriptor. In effect, the descriptor can be a type of virtual pharmacophore.

The determination of the three-dimensional structure of the gp120 with the extended V3 loop provides a basis for the design of new and specific compounds that are useful for eliciting an immune response. For example, from knowing the three-dimensional structure the stabilized form of gp120 or the gp120 with the extended V3 loop, computer modeling programs may be used to design or identify different molecules expected to interact with possible or confirmed active sites such as binding sites or other structural or functional features of neutralizing antibodies.

By way of example, a compound that potentially mimics the antigenic surface of the stabilized form of gp120 or the gp120 with the extended V3 loop can be examined through the use of computer modeling using a docking program such as GRAM, DOCK or AUTODOCK (see for example, Walters et al. Drug Discovery Today, 3(4):160-178, 1998; Dunbrack et al. Folding and Design 2:27-42, 1997). This procedure can include computer fitting of potential immunogens to ascertain how well the shape and the chemical structure of the potential binder will mimic the antigenic surface. Various other computer programs such as AMBER or CHARM may be used to further refine the dynamic and electrostatic characteristics of a candidate compound. Programs such as GRID (Goodford, J. Med. Chem, 28:849-57, 1985) may also be used to analyze the antigenic surfaces to predict immunogenic compounds. Alternatively, computer-assisted, manual examination can be used to predict immunogenic compounds from antigenic surfaces.

IX. Stabilized gp120 Polypeptides as Crystallization Tools

One problem with the formation of crystals containing wild-type gp120 is that conformationally variable molecules are not amenable to crystallization. For an ordered crystal to form the molecules forming the crystal must be essential locked in place. Molecules that are unstable or “floppy” such as wild-type gp120 must overcome large entropic (ΔS) costs to form a crystal lattice. By using conformationally stabilized forms of gp120 this entropic cost of becoming ordered is lessened and crystals form more easily. Those skilled in the art can take advantage of this by crystallizing their complex of interest with a stabilized form of gp120. For example, stabilized forms of gp120 can be used to crystallize previously uncrystallizable broadly neutralizing antibodies. In one embodiment, the broadly neutralizing antibody does not induce conformational stabilization as measured by −TΔS of less than 28 kcal/mol upon antibody binding to gp120. The use of broadly neutralizing antibodies is disclosed, for example, in Burton, Nature Re. 2:706-713, 2002, herein incorporated by reference. One example of how this can be accomplished is by forming complexes of a stabilized form of gp120 and the antibody of interest in the presence of CD4.

The following examples are provided to illustrate certain particular features and/or embodiments. These examples should not be construed to limit the invention to the particular features or embodiments described.

EXAMPLES Example 1 Structure-Assisted Stabilization of gp120 in its CD4-Bound Conformation

This example describes the methods used to design stabilized forms of gp120 disclosed herein.

Thermodynamic analysis showed that the conformation of gp120 prior to CD4 binding was highly flexible (Myszka et al., Proc Natl Acad Sci USA. 97(16):9026-31, 2000). The CD4-bound state of gp120 consists of an inner domain (containing the N and C termini), an outer domain, and a four-stranded bridging sheet minidomain. Two-thirds of the CD4 contact surface is with the outer domain, the remaining one-third with the bridging sheet. In the unliganded state, the inner domain is radically altered, with most of its secondary structural elements repositioned. The bridging sheet is pulled apart with the two β-hairpins of the sheet separated by 20 Å. The outer domain, by contrast, remains virtually unchanged.

An initial series of mutants was constructed and analyzed. Initial antigenic analysis suggested that a single mutation, 375 S to W, was able to partially stabilize gp120 in the CD4-bound state. Thermodynamic analysis (ITC) confirmed this result, showing that the entropy (−TΔS) of gp120 binding to CD4 had reduced from 40 kcal/mol to roughly 25 kcal/mol (Xiang et al., J Virol. 76(19):9888-99, 2002).

To further reduce the entropy of CD4 binding to a range typical of antibody recognition (5-10 kcal/mol), precise characterization was used to confirm the mutational stabilization of conformation including: (1) crystallographic determination of the gp120 mutant structure (2) isothermotitration calorimetric analysis of the entropy of CD4 binding, and (3) precise surface-plasmon resonance analysis of the on/off rates of antibodies to the modified gp120 glycoproteins. This design cycle is shown in FIG. 1. Initial isothermotitration calorimetry demonstrated that cavity-filling mutants, such as 375 S to W, did not significantly reduce the entropy of CD4 gp120 binding in the context of core HXBc2.

Additional cavity-filling mutations and five different disulfides were modeled. The cavity-filling mutants increased hydrophobic interactions at domain interfaces. The disulfides either tied together the inner domain, outer domain and bridging sheet, or were internal to the bridging sheet. Crystallographic analysis on five of these disulfides showed that four of them formed disulfide bonds. Two of these showed minimal perturbation in structure: 96-275 which tied together the inner and outer domain, 109-428 which tied together the bridging sheet and outer domain. The 231-267 disulfide, which tied together the inner domain and outer domain and the 123-431 disulfide, which tied together two strands of the bridging sheet, both showed local perturbations of structure. The potential disulfide formed by mutating 231 to C and 268 to C did not form (FIG. 2). The recently solved crystal structure of the unliganded gp120 core from SIV (Chen et al, Structure, 13(2):197-211, 2005) allowed the position of each disulfide to be modeled in the unliganded structure (FIG. 3). This mapping showed that even a single disulfide would be incompatible with the conformation of the unliganded gp120 seen in the SIV crystal structure (Table 3).

TABLE 3 Relative disulfide distances in the CD4-bound conformation and in the unliganded SIV conformation. Cα-Cα Cα-Cα Category HIV Mutation SIV Equivalent Distance (Å) Distance (Å) Category HIV Mutation SIV Equivalent HIV SIV S-S  96-275  78-290 6.4 21.9 S-S 109-428  91-441 6.1 16.2 S-S 123-431 105-444 4.4 23.5 S-S 231-267 245-282 6.0 16.8 Cavity 257/375 271/391 5.2 5.6

In the core context, each single inter-domain disulfide reduced the entropy of CD4 interaction by roughly 10 kcal/mol, as measured by isothermotitration calorimetry (ITC). Combinations of disulfides were tested. Two disulfide combinations showed similar antigenic phenotypes suggesting a partially stabilized gp120 conformation; ITC analysis for several of the different two disulfide combinations showed the entropy of CD4 interaction was reduced by roughly 20 kcal/mol. Combinations of three and four disulfides were also tested, although most of these only expressed poorly, perhaps due to complications of folding so many cysteines into the correct disulfide bonds. Removal of additional core disulfide (such as the second conserved disulfide in the V1/V2 region) and stabilization of the V3 region may enhance folding. A summary of the qualitative Biacore and ITC results for 17 mutants is shown in Table 4.

TABLE 4 Qualitative BIACORE on Supernatant and ITC results Mutant location Mutant C1 CD4/CD4i CD4BS DSC/T_(M) Name C2 C3 S1 S2 S3 S4 S5 CD4 17B M6 b12 F105 F91 15e m14 m18 SS folding ° C. WT A A A AA AA AA AA AA AA 0 FFFF 50.6 core*  2a* x AAA AA AA AA N N A/N A/N AA 0 FFFF 50.6  4-0* x x AAA AA AA AA N N A/N A/N AA 0 FFFF 55.7  4a* x x A A nd A/N N N N N A 1 FFF 53.8  4b* x x A A nd AA N A/N N N AA 1 FFF 56.4  4c* x x A A nd A N N N N AA 1 FFF  5mut x x A A nd A N N N N AA 1 FFF  6a* x x x A A nd AA N A N N AA 1 FFF  6b x x x AA A nd N N N N N N 2 FFF 59.0  8a x x x x AA A nd A N N N N AA 2 F  8b* x x x x AA A nd A N N N N A/N 2 FF  9a x x x x x A N N A/N N N N N N 3 F/N  8c x x x x A A A A/N N N N N N 3 F/N 10a x x x x x N N nd N N N N N N 3 N  9b x x x x A A A A/N N N N N AA 3 F/N 10c x x x x x A N N A/N N N N N AA 3 F/N  9c* x x x x AA AA AAA A N N N N A/N 3 F 10b x x x x x A A A/N A N N N N A/N 3 F/N 11a x x x x x A A A A N N N N N 4 F/N Note: Cavity-filling mutants: C1: M95W, C2: T257S/S375W; C3: A433M; Disulfide bond mutants: S1: W96C/V275C; S2: I109C/Q428C; S3: T123C/G431C; S4: K231C/E267C; S5: K231C/E268C Qualitative Biacore analysis and ITC of conformationally stabilized mutants. Biacore analyses were carried out on transfected cell supernatants or with purified protein at 10 ug/ml. Yellow rows represent mutants with structures determined by X-ray crystallography. “A” indicates binding, “F” indicates folding, and “N” indicates no binding or folding. The mutants are indicated with the wildtype residue and position followed by the substituted residue as follows, C1:M95W; C2:T275S/S375W; C3:A433M; S1:W96C/V275C; S2:I109C/Q428C; S3:T123C/G431C; S4K231C/E267C, for example A433M means that a methionine has been substituted for an alanine to create a C3 mutant protein.

Quantitative surface-plasmon resonance characterization of the binding of the various mutants to CD4, to 17b in the absence of CD4 and to 17b in the presence of CD4 allowed the degree of conformational stabilization to be assessed (Table 5).

TABLE 5 Quantitative Surface-Plasmon Resonance Characterization of Mutant gp120 Kinetic Parameters. CD4 17b without CD4 17b with CD4 CD4 Mutant on off KD on off KD on off KD Induction WT 4.95E+04 1.46E−03 2.95E−08 9.81E+03 4.33E−03 4.41E−07 7.84E+05 2.07E−03 2.64E−09 7.99E+01 core 2a 1.19E+05 1.78E−04 1.49E−09 1.03E+05 1.66E−02 1.61E−07 1.62E+06 9.98E−03 6.14E−09 1.57E+01 4-0 1.10E+05 1.39E−04 1.26E−09 1.54E+05 0.0196 1.28E−07 1.76E+06 0.0101 5.73E−09 1.14E+01 4a 1.23E+05 2.81E−04 2.28E−09 3.75E+05 0.0212 5.66E−08 2.51E+06 0.014  5.56E−09 6.69E+00 4b 1.08E+05 1.62E−04 1.50E−09 1.06E+05 0.0192 1.81E−07 1.48E+06 0.01  6.76E−09 1.40E+01 4c l.07E+05 1.20E−04 1.12E−09 2.98E+05 0.0114 3.82E−08 2.05E+06 9.14E−03 4.45E−09 6.88E+00 5mut 3.08E+04 4.14E−04 1.35E−08 7.06E+04 0.0168 2.37E−07 1.31E+06 1.02E−02 7.78E−09 1.86E+01 6a 6.56E+04 4.47E−04 6.82E−09 8.94E+04 8.42E−03 9.41E−08 2.83E+05 7.46E−03 2.64E−08 3.17E+00 6b 7.89E+04 3.08E−04 3.91E−09 2.08E+05 0.0225 1.08E−07 9.27E+05 0.0126 1.36E−08 4.46E+00 8a 141000 0.00062   4.4E−09 354000  0.00712 2.01E−08 240000 0.0106 4.42E−08 0.677966 8b  83000 0.000484 5.83E−09 135000  0.00403 3.01E−08 310000 0.0151 4.88E−08 2.296296 9c 6.78E+04 1.45E−04 2.14E−09 1.04E+06 0.011  1.05E−08 1.28E+06 8.53E−03 6.69E−09 1.23E+00

CD4-on rate did not change much, indicating that initial CD4 occurs without conformational stabilization. The off-rate did decrease relative to wild-type, however, indicating that once CD4 bound, the conformational change was able to lock CD4 into place. A very different effect was seen with the CD4i antibody 17b. With 17b, conformational stabilization greatly increased the “on-rate” of binding, with little effect on the off-rate. This indicated that 17b cannot bind to its site, without the conformational change induced by CD4. In contrast, the initial binding even of CD4 must occur without the conformational change.

Surface-plasmon resonance (SPR) experiments were performed on a Biacore biosensor system at 25° C. Antibody (17b or m6 for the CD4i antibodies; F105, b12, 1.5e, etc. for CD4BS antibodies; b3, b3, b11 etc. for Fab fragments of CD4BS antibodies; and 2-domain CD4 for CD4) were immobilized on research grade CM5 sensor chips using the recommended standard amine coupling. Binding experiments were carried out in HBSP buffer (10 mM HEPES, pH 7.4, 150 mM NaCl and 0.005% surfactant P-20).

During the association phase, gp120 were passed over the buffer-equilibrated chip surface at a rate of 30 ul/min. After the association phase, bound analytes were allowed to dissociate for 5 min. The chip surface was then regenerated by two 25 ul injections of 10 mM Glycine/HCl (pH 3.0) at a flow rate of 50 ul/min. Association and dissociation values were calculated by numerical integration and global fitting to a 1:1 interaction model using BIAevaluation 3.0 software (Biacore, Inc.)

Example 2 Atomic Level Structure Determination of gp120

This example describes the methods used to obtain crystals of a gp120 with an extended V3 loop.

Variational Crystallization and Robotic Screening

To increase the probability of obtaining crystals suitable for X-ray structural analysis, 13 different complexes of HIV-1 envelope glycoprotein gp120 core with intact V3 were prepared and screened for crystallization. To ensure that gp120 was in its coreceptor binding conformation, all complexes contained CD4 (2-domain).

1) Protein Production, Purification, and Complex Preparation

Constructs of core+V3 gp120 from clade B HIV-1 isolates, YU2, JR-FL, and HXBc2, were prepared as previously described (Wu et al., Nature 384:179, 1996; Grundner et al., Virology 330:233, 2004). Truncations of the N-terminus, C-terminus, and substitution of the tripeptide GAG for the V1/V2 region were identical to those previously described (Grundner et al., Virology 330:233, 2004). Wild-type isolates were used for YU2 and HXBc2. For JR-FL, a functional 2-glycan deletion variant was used with mutations, 301N/Q and 388T/A (Koch et al., Virology 313:387, 2003). This CCR5-using JR-FL variant was more susceptible to neutralization by CD4-binding site antibodies, but not to CD4-induced antibodies (Koch et al., Virology 313: 387, 2003. Constructs were expressed in Drosophila Schneider 2 cells under an inducible metallothionein promoter. The 2-domain CD4 (d1d2), antigen-binding fragments (Fabs) and single-chain variable fragments (scFv) of CD4-induced (CD4i) antibodies, 17b, 48d, 412d, m6, m9 and X5, were prepared as previously described (Ryu et al., Nature 348:419, 1990; Kwong et al., J. Biol. Chem. 274:4115, 1999; Huang et al., Proc. Natl. Acad. Sci. USA 101:2706, 2004; Zhang et al., J. Mol. Biol. 335:209, 2004; Moulard et al., Proc. Natl. Acad. Sci. USA 99:6913, 2002). Preparations of gp120 complexes followed procedures that were essentially the same as previously described (Kwong et al., J. Biol. Chem. 274:4115, 1999). Briefly, glycans were removed by digestion with endoglycosidases H and D to leave only the protein proximal N-acetylglucosamine and 1,6 fucose residues. The 2-domain CD4 was added, the binary complexes passed through a concanavalin A column to remove any gp120 proteins with uncleaved N-linked glycan, and the complexes further purified by gel filtration (Hiload 26/60 Superdex S200 prep grad, Amersham). Fab or scFv of CD4-induced (CD4i) antibodies were added and the ternary complexes purified by Superdex S200 chromatography. Purified complexes in 0.35 M NaCl, 2.5 mM Tris pH 7.0, 0.02% NaN3 were concentrated to 5-8 mg/ml. The following complexes were made (specified by strain of core+V3 gp120:soluble CD4 domain fragment:CD4-induced antibody type and fragment):

JR-FL:d1d2:17b Fab

JR-FL:d1d2:48d Fab

JR-FL:d1d2:412d Fab

JR-FL:d1d2:X5 Fab

JR-FL:d1d2

YU2:d1d2:48d Fab

YU2:d1d2:X5 Fab

HXBc2:d1d2:17b Fab

HXBc2:d1d2:48d Fab

HXBc2:d1d2:412d Fab

HXBc2:d1d2:X5 Fab

HXBc2:d1d2:m6 scFv

HXBc2:d1d2:m9 scFv

2) Robotic Screening of Crystallization Conditions

The gp120 complexes were screened robotically using vapor-diffusion sitting droplets composed of 50 nl protein combined with 50 nl crystallization solution (Lesley et al., Proc. Natl. Acad. Sci. USA 99:11664, 2002). 576 different commercially available crystallization solutions were used in each screen. JRFL complexes were screened with Hampton Research Screen I/II, Emerald Wizard Screen I/II, Emerald Wizard Cryo Screen I/II, Hampton Crystal Screen Cryo, Hampton PEG/Ion Screen, Hampton Grid Screens (ammonium sulfate, PEG 6000, MPD, and PEG/LiCl), and Syrrx Polymer Screen. YU2 and HXBc2 complexes were screened in the same manner except that the Hampton Research Index screen was substituted for the Emerald Wizard Cryo Screens. Pictures of crystallization drops were taken at 0, 1, 3, 7, 14, and 21 days after set-up, and the images inspected visually for protein crystals.

3) Crystallization Optimization

Initial crystals observed from robotic screens were reproduced and optimized manually using vapor-diffusion hanging droplets. A total of eight different crystal forms were grown to sizes suitable for testing diffraction quality. While most of the crystals diffracted to at best only 6-10 Å, one crystal consisting of JR-FL:d1d2:X5 Fab diffracted to at least 5 Å and was chosen for further optimization. Larger single crystals were produced by macroseeding (Thaller et al., J. Mol. Biol. 147:465, 1981): 1.5 μl of 5 mg/ml JR-FL:d1d2:X5 Fab was mixed with an equal volume of 1.3 M ammonium sulfate and placed over a 0.5 ml reservoir of 1.3 M ammonium sulfate; after 30 minutes, a single crystal was transferred directly to the droplet. Macroseeded crystals grew to 0.1×0.1×0.2 mm in 5-7 days.

Example 3 Structure Determination of gp120 with an Extended V3 Loop

This example describes the methods used to determine the structure of a gp120 with an extended loop to atomic resolution.

Data Collection

Crystals were dehydrated (Heras et al., Structure 11: 139, 2003) over 3 M ammonium sulfate reservoirs for 2-3 days. Dehydrated crystals were cross-linked over 20 μl of 1.5% glutaraldehyde for 1.5 hr using the procedure of Lusty (Lusty, J. Appl. Cryst. 32:106, 1999), transferred to a cryoprotectant solution containing 2 M ammonium sulfate, 60% (w/v) xylitol, 10% (w/v) erythritol and 5% (v/v) ethylene glycol for 1-2 minutes, covered with paratone-N, loop mounted, and flash-cooled to 100 K° for data collection. X-ray data were collected at a wavelength of 1.00 Å, using the intense 3rd generation undulator beam-line (SER-CAT) at the Advanced Photon Source, and processed and reduced with HKL2000 (Otwinowski and Minor, Methods Enymol. 276:307, 1997). The crystals were found to belong to space group P622 and to contain one complex per asymmetric unit. The diffraction was anisotropic, with stronger diffraction along the 6-fold axis. The crystal structure of JR-FL:d1d2:X5 Fab was solved by molecular replacement with CNS (Brunger et al., Acta Crystallogr. D 54:905, 1998). For gp120:CD4, a binary search model was constructed from YU2 core gp120 complexed to d1d2 as extracted from the previously determined ternary complex with 17b (pdb accession number, 1RZK) (Kwong et al., Structure 8:1329, 2000), with gp120 N-terminus (residues 83-86) and V4 region (residues 399-406) deleted. For X5 Fab, the structure of free X5 was used (pdb accession number, 1RHH) (Darbha et al., Biochemistry 43:1410, 2004). Cross-rotation and translation search with 15-4 Å data yielded Patterson correlation coefficients of 22.3% and 31.1% for YU2core:d1d2 and X5 Fab, respectively. The combined solution gave a Patterson correlation coefficient of 51.7%. By using the programs, O (Jones et al., Acta Crystallogr. A 47:110, 1991) for model building and CNS (Brunger et al., Acta Crystallogr. D54:905, 1998) for refinement, side-chains of the initial models were corrected, and the models subjected to torsion angle simulated annealing with slow cooling. Iterative manual fittings were carried out in B-value sharpened maps (−75 Å²; 2Fo−Fc) to enhance visual recognition of protein sidechain definition. Refinement in CNS, however, used unsharpened data, with strong 3 geometric constraints to maintain idealized stereochemistry. Statistics summarizing the X-ray crystallographic data and refinement are shown in Table 6.

TABLE 6 X-ray crystallographic data and refinement statistics Data collection Space group P622 Molecules per ASU 1 Wavelength, Å 1.00 Unit cell dimensions a = b = 226.0 Å, c = 98.0 Å Resolution, Å* 50-3.30 (3.71-3.55, 3.55-3.42, 3.42-3.30) Completeness, %* 86.6 (91.4, 50.7, 20.9) No. of total reflections 186,823 No. of unique reflections 19,372 Redundancy* 9.6 (5.1, 4.3, 3.1) I/σ* 26.2 (2.3, 1.5, 1.3) Rsym, %*, ‡ 8.2 (38.8, 47.3, 50.5) Refinement statistics (|F| > 0 σ) Resolution, Å 20.0-3.30 No. of reflections 19,364 Rcryst, %*, § 31.7 Rfree, %*, §, || 34.7 Rmsd bond length, Å 0.0043# Rmsd bond angles, ° 0.978# Luzzatti error, Å 0.64 Average B-value, Å2 125 Ramachandran plot Most favored, % 83.3 Additionally allowed, % 15.8 Generously allowed, % 0.8 Disallowed, % 0.1 *Values in parentheses are for the last three highest resolution shells. ‡ Rsym = Σ|I − <I>|/Σ<I>, where I is the observed intensity, and <I> is the average intensity of multiple observations of symmetry related reflections. § R = Σhkl||Fobs| − |Fcalc||/Σhkl|Fobs| || Rfree is calculated from 10% of the reflections excluded from refinement. #The geometry was tightly restrained, as this was observed to improve the Rfree. Model Analysis

All superpositions were performed using 1sqkab in CCP4 (Collaborative Computational Project, Acta Crystallogr. D50:760, 1994). Molecular surface interactions were calculated using MS (Connolly, J. Mol. Graph. 11:139, 1993). Figures were prepared using PyMOL (DeLano Scientific, San Carlos, Calif., 2002) and GRASP (Nicholls et al, Proteins Struct. Funct. Genet. 11:281, 1991).

Glycan Modeling

Asn-(N-acetylglucosamine)2(mannose)3 N-linked sugar cores were modeled following procedures described previously for the HXBc2 core (Wyatt et al., Nature 393:705, 1998). Briefly, JR-FL core with V3 and the HXBc2 core with modeled glycan were superimposed. Conserved sites of Nlinked glycan were transferred, and other sites were built manually, including glycans at 301 and 386. The core was fixed and the Asn and attached glycan were subjected to molecular dynamics.

Sequence Analysis

Analyses were carried out with only sequences with complete V3, limited to one sequence per individual, extracted from the Los Alamos HIV sequence database (hiv.lanl.gov/content/hiv-db) for all M group sequences that had coreceptor usage specified as either CCR5 or CXCR4. The B clade subset of the M group had the most coreceptor usage information for a single clade, and so it was also analyzed separately. Alignments were made from constant to variable regions, with the β-turn (GPGR analog) of the tip forced into alignment. The Shannon entropy (Shannon, Bell System Tech. 27:379, 1948) was calculated for each site, treating gaps inserted to maintain alignment and distinct amino acids as characters, and statistical analysis of the variation at each site comparing R5 and X4 viruses was performed by using a Monte Carlo randomization of the two data sets (Korber et al., J. Virol. 68:7467, 1994), with a Bonferroni correction to contend with multiple tests. An entropy score is actually a simple measure of the information content of a data set: when considered in this context, as a measure of amino acid diversity in the column of an alignment, it has the virtue of capturing both the range and distribution of observed amino acids. Zero indicates absolute conservation, and a score of 4.4 indicates complete randomness.

Example 4

This example describes the analysis of the structural details of a gp120 with an extended loop.

The third variable region (V3) of the HIV-I gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. Disclosed herein is the structure of the V3 loop in the context of an HIV-I gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 positions V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Snapshots of the gp120 entry mechanism have been visualized through crystal structures of unliganded and CD4-bound states (Chen et al., Nature 433:834, 2005; Kwong et al., Nature 393:648, 1998). Prior to this disclosure an essential component of the coreceptor binding site, the third variable region (V3), was been absent from structural characterizations of the gp120 core. The structure of V3 in the context of core gp120 bound to CD4, described herein, reveals the entire coreceptor binding site. The V3 appears to act as a molecular hook, not only for snaring coreceptor but also for modulating subunit associations within the viral spike. Its extended nature is compatible with the elicitation of an immunodominant antibody response and the generation of broadly neutralizing antibodies to V3 epitopes.

The extreme glycosylation and conformational flexibility of gp120 inhibit crystallization. Variational crystallization and various technologies adapted from structural genomics were used to obtain crystals suitable for x-ray structural analysis (Kwong et al., J. Biol. Chem. 274:4115, 1999; Stevens and Wilson, Science 293:519 (2001). The gp120 core with V3 from JR-FL The crystallized JR-FL was derived from a JR-FL variant with two point mutants, Asn301Gln and Thr388Ala. These mutations removed two Nlinked glycans, and the resultant virus was more sensitive to neutralization but was otherwise functional (Koch et al., Virology 313:387, 2003), when complexed to CD4 (two domain) and the antigen-binding fragment (Fab) of the X5 antibody (Koch et al., Virology 313:387, 2003), formed hexagonal crystals that diffracted to approximately 3.5 Å resolution with x-rays provided by an Advanced Photon Source undulator beam line (SER-CAT) (Table 5). The structure was solved by molecular replacement and is shown in FIG. 5.

The overall assembly of CD4, X5, and core gp120 resembled the previously determined individual structures of CD4 (Ryu et al., Nature 34:419, 1990; Wang et al., Nature 348:411, 1990) and of free X5 (Darbha et al., Biochemistry 43:1410, 2004) as well as the complex of core gp120 bound to CD4 (Kwong et al., Nature 393:648, 1998; Kwong et al., Structure 8:1329, 2000). For core gp120, some differences were observed in the variable loops and also at the N terminus, regions where variations in gp120 have previously been observed (Chen et al., Nature 433:834, 2005; Kwong et al., Nature 393:648, 1998; Kwong et al., Structure 8:1329, 2000; Huang et al., Structure 13:755, 2005). Structural resemblance was maintained around the base of V3, indicating that the previous truncation (Chen et al., Nature 433:834, 2005; Kwong et al., Nature 393:648, 1998; Kwong et al., Structure 8:1329, 2000; Huang et al., Structure 13:755, 2005) did not distort this region of the core. In X5, a large structural difference was observed for the third complementarity determining loop of the X5 heavy chain (CDR H3). Comparison of the refined structures of free X5 (Darbha et al., Biochemistry 43:1410, 2004) and bound X5 showed Ca movements of up to 17 Å, one of the largest induced fits observed for an antibody (FIG. 9). The gp120 envelope protein is composed of inner and outer domains, named for their expected orientation in the oligomeric viral spike (Kwong et al., Nature 393:648, 1998). V3 emanates from neighboring staves of the stacked double barrel that makes up the outer domain; it is almost 50 Å long from the disulfide bridge at its base to its conserved tip, but is otherwise only 15 Å wide and 5 Å deep (FIG. 6). Overall, it can be subdivided into three structural regions: a conserved base, which forms an integral portion of the core; a flexible stem, which extends away from the core; and a b-hairpin tip. In the crystal structure, the flexibility and position of the V3 tip may be influenced by a lattice contact, in which hydrogen bonds are made to the exposed backbone of the V3 b ribbon between Ile307 and Ile309. Tenuous side-chain contacts are also observed for the returning strand in the V3 stem with X5, as well as with V4 of a symmetry-related gp120 molecule, but these side-chain contacts are unlikely to influence its conformation. Features of gp120 important for coreceptor binding have been mapped by mutagenesis to two regions: (i) the V3 tip, and (ii) the gp120 core around the bridging sheet, the V3 base, and neighboring residues (Rizzuto et al., Science 280:1949, 1998; Rizzuto and Sodroski, AIDS Res. Hum. Retroviruses 16:741, 2000; Cormier et al., J. Virol. 75:5541, 2001; Cormier et al., J. Virol. 76:8953, 2002). Analysis of these two regions on this new structure indicates that they are conserved in both sequence and structure (FIGS. 10A and 11). The structural conservation of the V3 tip was surprising here in light of the apparent flexibility of the intervening stem, but we found the V3 tip to be strikingly similar in the context of the core, in antibody-V3 peptide complexes, and as a free peptide; such similarity is consistent with previous reports of recurring conformations for the V3 tip in antibody:peptide complexes (Stanfield et al., Virology 315:159, 2003). The structure shows that conserved regions important for coreceptor binding are separated by 10 to 20 Å and by portions of the V3 stem with moderate to high sequence variation (FIG. 10). Emerging data on the structures of the coreceptors indicate that the regions identified as being important for binding gp120—the coreceptor N terminus and the second extracellular loop—may also be spatially separated (Klco, et al., Nat. Struct. Mol. Biol. 12:320, 2005).

By integrating the two-site gp120 binding site on the coreceptor with the two-site coreceptor binding site that it is observe in the structure of V3 gp120 with an extended V3 loop, that the N terminus of the coreceptor reaches up and binds to the core and V3 base while the V3 tip of gp120 reaches down to interact with the second extracellular loop of the coreceptor (FIG. 7B). Support for this model comes from several sources: (i) Biochemical studies show that the binding of CCR5 Nterminal peptides to gp120 is affected by gp120 alterations only on the core and around the base of V3 (Cormier and Dragic, J. Virol. 76:8953, 2002); and (ii) small-molecule inhibitors of HIV entry that bind to the second extracellular loop of the coreceptor are observed to no longer affect mutant viruses with V3 truncations. Despite general tolerance of the V3 stem to changes in sequence, there is less tolerance for insertions or deletions than in other gp120 variable loops. Superimposition of the core gp120 V3 structure on the modeled gp120 core trimer that previously obtained by optimization of quantifiable surface parameters (Kwong, et al., J. Virol. 74:1961, 2000) orients gp120 in the context of both cell-surface CD4 and the target cell membrane. Such a superposition projects the highly conserved Pro-Gly of the V3 tip 30 Å toward the target cell membrane (FIG. 7A). Different coreceptors, primarily CXCR4 or CCR5, can support HIV-1 entry. Sequence analysis has defined an 11/25 rule: If the 11th or 25th positions of V3 are positively charged, viruses will use CXCR4; otherwise they use CCR5 (Resch et al., Virology 288:51, 2001). In addition, V3 sequences are more conserved for CCR5-using viruses (FIG. 10). The structure of the V3 loop disclosed herein shows that positions 11 and 25 (residues 306 and 322) are within the variable stem. They each project about the same distance away from the core but are separated by a Ca distance of 17 Å (FIG. 10). This separation suggests that positions 11 and 25 recognize different portions of the coreceptor. CD4 induces large conformational changes in gp120. Before CD4 binding, V3 may not protrude precisely as observed here for the CD4-triggered coreceptor binding state of gp120 (Sattentau and Moore, J. Exp. Med. 174:407, 1991; Werner and Levy, J. Virol. 67:2566, 1993 ). However, structural comparison of unliganded versus CD4-bound conformations of gp120 (Kwong et al., Nature 393:648, 1998; Hartley et al., AIDS Res. Hum. Retroviruses 21:171, 2005) reveals that the local conformation of the region of the outer domain from which V3 emanates is mostly unchanged. Thus, the extended structure of V3 that we observe here should be generally representative of V3. Immunization with gp120 or gp120/gp41 in various contexts may elicit an immune response in which virtually all of the neutralizing activity is directed at V3. The conformation of crystal and nuclear magnetic resonance structures of V3−reactive antibody-peptide complexes was examined for clues to this immunodominant response (FIG. 11). Although the conformation of V3 peptides in these antibody-peptide complexes varies somewhat, the Pro-Gly tip is more conserved. Superimposing the conserved tip in the peptides with the V3 tip in the core+V3 structure permits the V3 peptide-binding antibodies to be placed in the context of the gp120 core. The antibodies completely surround V3 (FIG. 8). Although the accessibility of V3 may be quite different on a primary isolate in its pre-CD4 trimeric state, the extended nature of V3 as disclosed herein, when coupled to mechanisms that cloak the rest of the HIV envelope from antibody binding (Wyatt and Sodroski, Science 280:1884, 1998; Wyatt et al., Nature 393:705, 1998; Wei et al., Nature 422:307, 2003), is consistent with its ability to generate an immunodominant response. The attributes observed for V3 (such as, high relative surface area, chemically reactive backbone, conformational flexibility, and overall extended nature) may allow V3 to serve as a general molecular hook. Before CD4 binding, these attributes would enhance the ability of V3 to grasp neighboring protomers on the viral spike. Such quaternary interactions would explain V3's influence on overall neutralization sensitivity, for example, its ability to transfer neutralization resistance from YU2 to HXBc2 (Sullivan et al., J. Virol. 72:6332, 1998). After CD4 binding, the coreceptor binding site forms and V3 would jut prominently toward the target cell membrane. In this context, binding at the V3 tip may act as a ripcord to initiate gp41-mediated fusion.

Example 5 Prime-Boost Immunization with Stabilized gp120 and gp140 Trimer

This example describes the “prime-boost” immunization scheme used to generate a heightened immune response in a subject.

Based on the biophysical characterization of gp120 stabilized in the CD4 bound conformation performed an immunization scheme was performed whereby HXBc2 strain wild-type or cysteine-stabilized core gp120 proteins were used to prime the immune response for subsequent immunization with soluble, stabilized trimeric YU2 strain gp140-foldon molecules (Yang et al. J Virol. 76(9):4634-42, 2002). B-cells primed by the stabilized cores were primed for epitopes displayed preferentially only on the stabilized HX core CD4 binding site, or to other stabilized surfaces, efficiently presented only by the cysteine-stabilized cores.

Boosting with the gp140 trimeric molecules “immuno-focuses” primed B cells on shared and conserved determinants between the two immunogens and altering strains would not boost B cells directed at HX- or YU2-specific epitopes. Thus, the only B-cells boosted selectively by the trimer would be those that could bind efficiently both the stabilized core as well as the trimer. Thus, stabilized cores can stimulate B cells that could induce the CD4-bound or the b12 conformation in the gp140 trimers.

Based upon this scheme, HIV gp120 core and trimer proteins were expressed by transient transfection of 293 cells with the relevant plasmid DNA. Soluble proteins were purified from culture supernatants by affinity chromatography and maintained in PBS, pH 7.4. Each rabbit was injected at two sites by the intramuscular route in the hind leg with 50 ug of protein emulsified at 1:1 ratio in GSK AS01B adjuvant in a total volume of 1 ml. The rabbits were inoculated four times with emulsified HX wild-type or stabilized core proteins followed by two injections with the emulsified YU2 gp140 trimeric proteins. Inoculations were performed at approximate four week intervals and the immune sera were collected ten days following each injection. The presence of high-titer anti-gp120 antibodies were confirmed by ELISA. The ability to neutralize viral particles derived from selected HIV strains was determined in a luciferase-based HIV entry assay. Virus was incubated with pre- or post-immune sera and the percent neutralization in the immune sera was calculated as the decrease in entry relative to virus incubated with pre-immune sera or an irrelevant BSA protein-emulsified control. The tabulated results of the immunogenicity-neutralization are shown in FIG. 4A-B.

Example 6 Virus Neutralization

This example describes the neutralization of various HIV isolates with CD4 induced triggering.

Construction of DNA and Recombinant Adenoviruses

Plasmid DNA and Ad5-based first-generation (ΔE1, ΔE3) recombinant adenoviruses expressing different V loop deletions of gp140(ΔCFI) were constructed. HIV envelope genes encoding gp145(ΔCFI) (BaL) (Genbank accession No. M68893), gp145(ΔCFI) (clade C) (Genbank accession No. AF286227), gp145(ΔCFI) (CN54) (Genbank accession No. AX149771), and gp145(ΔCFI) (clade A) (Genbank accession No. U08794) were synthesized using human-preferred codons. gp145 (ΔCFI)(B)(V3/C/1AB) and gp145 (ΔCFI)(B)(V3/A/1AB) were made by replacing Ba1 V3 loop with shortened clade C V3(1AB) and clade A V3(1AB) sequences respectively.

Vaccination

Guinea pigs were intramuscularly immunized with 500 μg (in 400 μl PBS) of the gp145 version of plasmid DNA at week 0, 2, and 6. At week 14, the guinea pigs were boosted with 10¹¹ particles (in 400 μl PBS) of recombinant replication defective adenovirus (rAd) expressing the corresponding gp140 version of the protein. Serum was collected at week −2 and week 16, aliquotted, and frozen at −20° C.

Virus Neutralization Assay

Single round of infection HIV-1 Env pseudoviruses were prepared by cotransfecting 293T cells with an Env expression plasmid containing a full gp160 env gene and an env-deficient HIV-1 backbone vector (pSG3ΔEnv). Virus-containing culture supernatants were harvested 2 days after transfection, centrifuged and filtered through 0.45-micron filter, and stored at −80° C. Pseudovirus neutralization was measured as a function of Tat-induced luciferase reporter gene expression after a single round of infection in TZM-bl cells. TZM-bl cells express CD4, CXCR4 and CCR5 and contain and integrated reporter gene for firefly luciferase under the control of an HIV-1 LTR. The level of viral infection was quantified by measurement of relative luciferase units (RLU) that are directly proportion to the amount of virus inputs. Briefly, 40 ul of virus was incubated for 30 minutes at 37° C. with serial dilutions of test serum samples (10 ul) in duplicate wells of a 96-well flat bottom culture plate. The final serum dilution was defined at the point of incubation with virus supernatant. 10,000 TZM-bl cells were then added to each well in a total volume of 20 ul and plates were incubated overnight at 37° C. in a 5% CO2 incubator. One set of eight wells received mock antibody followed by virus and cells (controls wells for virus entry) and a set of eight wells received cells with mock virus (to control for luciferase background). Viral input was set at a multiplicity of infection (moi) of approximately 0.1, which generally results in 100,000 to 400,000 RLU. After over night incubation, 150ul of fresh medium was added to each well and incubated for 24 hours at 37° C. in a 5% CO₂ incubator. To determine RLU, cell culture medium was aspirated from wells followed by addition of 50 ul of cell lysis buffer (Promega, Madison, Wis.). 30 ul of cell lysate was transferred to wells of a black Optiplate (PerkinElmer) for measurement of luminescence using a Perkin-Elmer Victor-light luminometer that injects 50 ul of luciferase substrate reagent to each well just prior to reading RLU. To test for sCD4 triggering, two-domain sCD4 was added to the virus just prior to the addition of sera.

Example 7 Identification of Immunogenic Fragments of gp120

This example describes the selection of immunogenic fragments of stabilized gp120.

A nucleic acid molecule encoding a stabilized p120 fragment is expressed in a host using standard techniques (see above; see Sambrook et al., Molecular Cloning; A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, N.Y.: 1989). Preferable gp120 fragment is expressed such that the gp120 fragment can be isolated or purified in sufficient quantity. The stabilized gp120 fragment that are expressed are analyzed by various techniques known in the art, such as immunoblot, and ELISA, and for binding to CD4 and mAbs directed to the CD4 binding site, for example the b12 antibody.

To determine the antigenic potential of stabilized p120 fragments, subjects such as mice, rabbits or other suitable subjects are immunized with stabilized p120 fragments. Sera from such immunized subjects are tested for antibody activity for example by ELISA with the expressed polypeptide. They are also tested in a CD4 binding assay, for example by qualitative biacore, and the binding of neutralizing antibodies, for example by using the b12 antibody. Thus, antigenic fragments of stabilized forms are selected to archive broadly reactive neutralizing antibody responses.

Example 8 Conformational Masking of Stabilized Immunogens

This example describes the strategies to mask portions of a stabilized gp120 polypeptide from non-neutralizing antibodies.

The polypeptide “new 9c” as set forth as SEQ ID NO: 1 includes residues at the base of the V3 loop, and restores recognition of the core by the CD4-induced antibodies, such as 17b. Individual and combination glycan mutations were designed in the context of the stabilized gp120 polypeptides disclosed herein (for example, such as set forth in SEQ ID NO: 2 or encoded by SEQ ID NO: 4-18) to prevent the elicitation of non-neutralizing antibodies. Using site-directed mutagenesis, specific Asn and Ser/Thr residues are incorporated into the 8b core. The Asn-X-Ser/Thr residues mediate the attachment of glycans to the designated asparagine residues by mammalian cell glycosylating enzymes in the endoplasmic reticulum. This scheme is used to mask the immunogenic but non-neutralizing surfaces present in gp120.

Typically, wild-type gp120 cores elicit antibodies in rabbits that bind more efficiently to the core proteins than to full length gp120 glycoproteins. It is likely that the cores, via their truncated loops and N- and C-termini, elicit antibodies to surfaces that are not exposed in monomeric gp120.

As another aspect of an overall strategy to optimize the stabilized core priming of a trimer boost, glycans are designed at selected densities on the stabilized core to dampen or eliminate unwanted core-specific responses based upon the 8b core-b12 structure disclosed herein. The optimized and proteins are expressed, purified, analyzed and tested for immunogenicity by themselves or in sequential prime-boost with the YU2 gp140 trimers.

To mask the surface recognized by 17b and other CD4-induced antibodies the following mutations were designed:

-   Mutation 1:Mutation 2 -   a. R419N:K421S -   b. I420N:Q422S -   c. Q422N:I424T -   d. I423N:N425T     and one additional mutant to add 2 glycans -   e. R419N:K421S+I423N:N425T

To mask surfaces other than the CD4 binding site, which includes the b12 epitope region, the following N-glycan addition sites were designed:

Glycan Location Mutation 1 Mutation 2 1 246 Q246N 2 267 E267N E269T 3 97 K97N D99T 4 103 Q103N H105S 5 92 N94T 6 114 Q114N L116T 7 222 G222N A224T 8 201 I201N Q203T 9 206 P206N V208T 10 423 I423N N425T 11 434 M434N A436S 12 442 Q442N R444T 13 210 F210N P212T

Density 2

Glycan Location Mutation 1 Mutation 2 1 246 Q246N 2 97 K97N D99T 3 103 Q103N H105S 4 201 I201N Q203T 5 206 P206N V208T 6 434 M434N A436S 7 442 Q442N R444T 8 210 F210N P212T 9 114 Q114N L116T

Density 3

Glycan Location Mutation 1 Mutation 2 1 206 P206N V208T 2 442 Q442N R444T 3 114 Q114N L116T 4 246 Q246N 5 434 M434N A436S Mutation 1 and Mutation 2 correspond to the N glycosylation consensus sequence: NxT/S where x is anything except proline. T is better than S for glycosylation. Blanks indicate positions where no mutations are necessary. These glysolated peptides are used to induce a immune response in a subject.

In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as limiting the scope of the invention. Rather, the scope of the invention is defined by the following claims. We therefore claim as our invention all that comes within the scope and spirit of these claims. 

1. An isolated nucleic acid comprising a nucleotide sequence encoding a wild type HIV-1 gp120 polypeptide, or immunogenic fragment thereof, comprising substitutions of cysteines for the amino acids in at least one of residue pairs 96 and 275; 109 and 428; 123 and 431; and 231 and 267, and amino acid substitutions at positions 257 and 375, wherein the polypeptide, or fragment thereof further comprises a tryptophan at position 95 if the polypeptide, or fragment thereof comprises cysteines at residue pairs 96 and 275, and wherein the residue numbers correspond to amino acid positions in the amino acid sequence set forth as SEQ ID NO:
 27. 2. The isolated nucleic acid of claim 1, comprising a nucleotide sequence set forth as one of SEQ ID NOs: 4-9, 11-18, or 26 or a degenerate variant thereof
 3. The isolated nucleic acid of claim 2 operably linked to a promoter.
 4. A vector comprising the nucleic acid of claim
 3. 5. An isolated host cell comprising the vector of claim
 4. 6. A composition comprising a nucleic acid molecule of claim 1 and a carrier.
 7. A method for generating an immune response in a subject, comprising administering to the subject the nucleic acid molecule of claim 1, thereby generating the immune response.
 8. The method of claim 7, further comprising administering to the subject a polypeptide or a nucleic acid molecule encoding: a) monomeric or trimeric gp140 of HIV envelope polypeptide; b) an unmodified monomeric or trimeric gp120 of HIV envelope polypeptide; or c) any combination of a-b, above.
 9. An isolated nucleic acid molecule comprising the nucleotide sequence encoding the amino acid sequence set forth as SEQ ID NO:
 2. 10. The isolated nucleic acid of claim 9, operably linked to a promoter.
 11. A vector comprising the nucleic acid of claim
 10. 12. An isolated host cell comprising the vector of claim
 11. 13. A composition comprising the isolated nucleic acid molecule of claim 9 and a carrier.
 14. The method of claim 7, further comprising administering a polypeptide or a nucleic acid expressing a polypeptide selected from the group consisting of: a) monomeric or trimeric gp140 of HIV envelope polypeptide; b) an unmodified monomeric or trimeric gp120 of an HIV envelope polypeptide; c) a soluble form of CD4; or d) any combination of a-c, above.
 15. The isolated nucleic acid of claim 1, wherein the nucleotide sequence encodes gp120 Hxbc core of SEQ ID NO: 20 having substitutions of cysteines for the amino acids at positions 96, 109, 275, and
 428. 16. The isolated nucleic acid of claim 1, wherein the nucleotide sequence encodes gp120 Hxbc core of SEQ ID NO: 20 having substitutions of cysteines for the amino acids at positions 96, 109, 275, and 428, a tryptophan for the methionine at position 95, a serine for the threonine at position 257, a tryptophan for the serine at position 375, and a methionine for the alanine at position
 433. 17. The isolated nucleic acid of claim 16, comprising the nucleic acid sequence set forth as SEQ ID NO: 10 or a degenerate variant thereof.
 18. The isolated nucleic acid of claim 16, comprising the nucleic acid sequence set forth as SEQ ID NO:
 10. 19. The isolated nucleic acid of claim 15, operably linked to a promoter.
 20. A vector comprising the nucleic acid of claim
 19. 21. A isolated host cell comprising the vector of claim
 20. 22. The isolated nucleic acid of claim 16, operably linked to a promoter.
 23. A vector comprising the nucleic acid of claim
 22. 24. A isolated host cell comprising the vector of claim
 23. 